bims-micgli Biomed News
on Microglia
Issue of 2026–03–15
33 papers selected by
Matheus Garcia Fragas, Universidade de São Paulo
  1. Control of microglial dynamics by the Arp2/3 complex and the autism- and schizophrenia-associated protein CYFIP1.
  2. ApoE4 Drives Microglial Lipid Dysregulation in Alzheimer's Disease via Epigenetic Reprogramming of the Asxl1/LXRα-H3K4me3 Axis.
  3. Microglia protein profiles in CSF across Alzheimer's disease clinical stages.
  4. Brain-engrafted monocyte-derived macrophages from blood and skull-bone marrow exhibit distinct properties.
  5. Transcriptional Remodeling of Microglia After Experimental Myocardial Infarction.
  6. Microglial NCAM1 attenuates ischemic brain injury by inhibiting NF-κB-driven neuroinflammation through IκBα stabilization.
  7. microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer's disease patients.
  8. Simultaneous spatial transcriptomics and morphology profiling as tools to explore how microglia change with age.
  9. Cerebrospinal fluid NPTX1 and NPTXR predict neurodegeneration and clinical progression in Alzheimer's disease.
  10. A central role for fibrinogen in promoting microglial repair of the hypoxia-disrupted blood-brain barrier.
  11. Replacing the immune system of the brain.
  12. Multi-modal dissection of cell-type specific TDP-43 pathology in the motor cortex.
  13. Macrophage-glia interactions regulate immune damage to enteric neurons during West Nile virus infection.
  14. Persistent microglial activation following neonatal CMV infection mediates neurodegeneration.
  15. Blood phosphorylated tau elevation as a biomarker in immunoglobulin light chain and transthyretin amyloidosis.
  16. Microglial cathepsin B is necessary for neuronal efferocytosis in zebrafish and mice during brain development.
  17. Impaired α-Synuclein aggregate clearance in neuronal cells drive their spread to microglia through tunneling nanotubes.
  18. Targeting Apolipoprotein E4 rescues photoreceptor degeneration by inhibiting the disease-associated microglia activation in experimental retinal detachment.
  19. TDP-43 pathology triggers neuroinflammation and cognitive impairment by inducing microglial necroptosis.
  20. Dual association patterns between microglial activation and neuronal health in Alzheimer's disease: a whole-brain MRSI/PET study.
  21. CSF microtubule-associated protein 1 light chain 3A and 3B levels are associated with tau pathology and Alzheimer's disease risk through amyloid deposition and microglial signaling.
  22. CAR T cell therapy in autoantibody-mediated neurological disorders: a promising strategy.
  23. Extracellular Vesicles Secreted by Human Microglia Support Blood-Brain Barrier Function Under Both Physiological and Inflammatory Conditions.
  24. Immune cells regulate circulating adipocyte extracellular vesicle levels in response to metabolic shifts.
  25. The neuromodulatory fragility hypothesis of Alzheimer's disease pathogenesis.
  26. Tumor immunogenicity shapes CNS immune niches and CD8⁺ T cell fate in glioblastoma.
  27. A human cerebral organoid model of West Nile virus encephalitis shows innate immunocompetency.
  28. The Interferon-miR-146a-5p-Stat1/Nrf2 Pathway Mediates LRRK2-R1441G-induced M1 over M2 Microglia Activation.
  29. Motoneurons inhibitory synapses homeostatically respond to neuronal activity and modulate Amyotrophic Lateral Sclerosis pathogenesis.
  30. Polyunsaturated Fatty Acid Balance Modulates Microglial State in a Murine Model of Oxygen-Induced Neovascularization.
  31. Immune imbalance between T helper 1, T helper 17 and regulatory T cells fuels amyotrophic lateral sclerosis pathogenesis: disease trajectory, diagnosis and therapeutic implications.
  32. Sleep deprivation exhibits an age-dependent effect on infraslow global brain activity.
  33. Amyloid-β and Mitochondrial Membranes: A Missing Link in Alzheimer's Pathogenesis.
  1. Proc Natl Acad Sci U S A. 2026 Mar 17. 123(11): e2532488123
    Control of microglial dynamics by the Arp2/3 complex and the autism- and schizophrenia-associated protein CYFIP1.
    James Scott-Solache, Jiaxin Pei, James Drew, Guillermo López-Doménech, Renaud B Jolivet, Manuela Nieto-Rostro, Elizabeth C Davenport, I Lorena Arancibia-Cárcamo, David Attwell, Josef T Kittler.
      Microglia use a highly complex and dynamic network of branched processes to sense and respond to their surroundings. Despite emerging evidence that microglial motility plays important roles in brain development, neurodegeneration, and neuropsychiatric disease, little is known about the intracellular machinery orchestrating microglial process dynamics. Here, we identify roles for regulators of the actin cytoskeleton in controlling microglial behavior. We show that the actin branching Arp2/3 complex is critical for maintaining microglial morphology and is required for surveillance but not chemotactic motility. Neuropsychiatric disease-associated CYFIP1, a core component of the WAVE regulatory complex linking upstream signaling pathways to activation of the Arp2/3 complex, is highly expressed in microglia but has an unknown function. We report that conditional deletion of Cyfip1 in mouse microglia reduces their morphological complexity and surveillance of the brain parenchyma, with no effect on chemotaxis. Deletion of Cyfip1 also increased microglial CD68 positive lysosome volume and engulfment of presynapses. Thus, actin remodeling by CYFIP1 and the Arp2/3 complex controls microglial dynamics and shifts microglia away from a homeostatic state with potential implications for neuropsychiatric disease.
    Keywords:  15q11.2; WRC; glia; neuroinflammation; phagocytosis
    DOI:  https://doi.org/10.1073/pnas.2532488123
  2. J Neuroinflammation. 2026 Mar 11.
    ApoE4 Drives Microglial Lipid Dysregulation in Alzheimer's Disease via Epigenetic Reprogramming of the Asxl1/LXRα-H3K4me3 Axis.
    Lanyan Lin, Zhen Pan, Zhen Wei, Xiulong Jiang, Yongxing Lai, Mingfeng Chen, Fan Lin.
      
    Keywords:  Alzheimer’s disease; ApoE4; Asxl1; Epigenetics; H3K4me3; Lipid droplets; Microglia
    DOI:  https://doi.org/10.1186/s12974-026-03740-3
  3. Nat Aging. 2026 Mar 11.
    Microglia protein profiles in CSF across Alzheimer's disease clinical stages.
    DELCODE Consortium
      Microglia are implicated in the progression of Alzheimer's disease (AD) pathology from its earliest stages, suggesting that cerebrospinal fluid (CSF) microglia profiling across clinical AD stages can aid in treatment development and monitoring. We analyzed two CSF cohorts (n = 834) that span from unimpaired controls to preclinical and dementia AD stages, identifying 109 dysregulated microglia-related proteins. Enrichment analyses revealed innate immune processes and cellular recruitment in preclinical AD, whereas AD dementia revealed adaptive immunity and macrophage responses. Next, we aligned the in vivo microglia protein profiles with ex vivo-derived microglial transcriptomic signatures, such as disease-associated microglia phenotypes. Transcriptomic signatures were not specific to either clinical stage but spanned both. We classified an 18-protein panel highlighting distinct changes between the preclinical and dementia stages. Our findings underscore the potential of microglia-based biomarker research for AD staging, offering insights into microglia dynamics in clinical AD stages and how transcriptomic signatures translate to proteomic profiles.
    DOI:  https://doi.org/10.1038/s43587-026-01088-0
  4. Neuron. 2026 Mar 11. pii: S0896-6273(26)00057-7. [Epub ahead of print]
    Brain-engrafted monocyte-derived macrophages from blood and skull-bone marrow exhibit distinct properties.
    Siling Du, Feiya Ou, Antoine Drieu, Eric Z Xu, Yumeng Cheng, Steffen E Storck, Tornike Mamuladze, Jay Cao, Nora Abduljawad, Bishan Bhattarai, Justin Rustenhoven, Niall Mortimer, Simone Brioschi, Khai Nguyen, Patrick Fernandes Rodrigues, Igor Smirnov, Daniel Gibson, J Michael White, Wandy Beatty, David DeNardo, Qingyun Li, Michael Meers, Claudia Z Han, Na Sun, Florent Ginhoux, Marina Cella, Marco Colonna, Jonathan Kipnis.
      Microglia arise from yolk sac progenitors and are thought to persist throughout life with minimal input from adult hematopoiesis. However, whether brain-engrafted monocyte-derived macrophages (MDMs) exist at homeostasis and during turnover and how they function relative to yolk-sac-derived microglia (YSMs) remain unsettled. Here, we combine lineage tracing, pharmacological microglia depletion, and multi-omics profiling to define the ontogeny, identity, and function of brain parenchymal macrophages. Despite sharing the parenchymal milieu, MDMs display transcriptional and epigenetic landscapes distinct from YSMs. Fate-mapping reveals that brain-engrafted MDMs transiently express CD206, echoing a developmental stage of microglial precursors. MDM engraftment and polarization are modulated by interleukin (IL)-34 and C-C chemokine receptor 2 (CCR2). Furthermore, parabiosis and skull-flap transplantation reveal that both blood and skull marrow supply the niche, yielding origin-biased MDM states. Functionally, MDM engraftment enhances cuprizone-mediated demyelination. Together, our study defines the origins, molecular features, and context-dependent roles of brain parenchymal macrophages across homeostasis, turnover, and central nervous system (CNS) pathology.
    Keywords:  macrophage ontogeny; microglia; monocyte; monocyte-derived macrophages; skull-bone marrow
    DOI:  https://doi.org/10.1016/j.neuron.2026.01.032
  5. Int J Mol Sci. 2026 Feb 27. pii: 2257. [Epub ahead of print]27(5):
    Transcriptional Remodeling of Microglia After Experimental Myocardial Infarction.
    Jan Traub, Nico Hofmann, Clément Cochain, Giuseppe Rizzo, Antoine-Emmanuel Saliba, Tobias Krammer, Stefan Frantz, Ulrich Hofmann, Katrin Sinning, Martin Vaeth, Anna Frey.
      Beyond cardiac impairment, myocardial infarction (MI) affects the central nervous system (CNS), where it has been associated with neuroinflammation and cognitive dysfunction. Microglia, the resident immune cells of the CNS, are key regulators of neuroinflammatory processes. However, the transcriptional landscape of microglia following MI remains incompletely understood. We hypothesized that MI induces transcriptional remodeling in microglia that may reflect altered metabolic regulation. Male C57BL/6J mice underwent permanent LAD ligation or sham surgery. Five days post-MI, CD45-intermediate and SiglecH/CD11b-positive immune cells were isolated from cortical and subcortical regions by FACS and subjected to single-cell RNA sequencing. Complementary exploratory metabolic assays included assessment of mitochondrial mass and membrane potential as well as glucose uptake. Microglia represented the predominant immune cell population in both the cortex and subcortex. Subclustering revealed a significantly increased proportion of a "low translational" microglial subset after MI. Pseudobulk differential expression and gene set enrichment analyses demonstrated significant downregulation of translation-related pathways in cortical microglia and proteostasis-associated pathways in subcortical microglia. These transcriptional changes were accompanied by a significant reduction in mitochondrial mass and metabolic observations consistent with altered energetic regulation, although several functional readouts did not reach statistical significance. Experimental MI is associated with region-specific transcriptional remodeling of microglia, characterized by reduced expression of energy-intensive and proteostasis-related pathways. Exploratory metabolic observations are consistent with altered energetic regulation but require confirmation in adequately powered studies. These findings suggest that systemic cardiac injury is linked to microglial transcriptional adaptation in the early post-infarction phase.
    Keywords:  CNS; metabolism; microglia; myocardial infarction; neuroinflammation
    DOI:  https://doi.org/10.3390/ijms27052257
  6. J Neuroinflammation. 2026 Mar 14.
    Microglial NCAM1 attenuates ischemic brain injury by inhibiting NF-κB-driven neuroinflammation through IκBα stabilization.
    Zongdong Yu, Luli Yu, Wei Lu, Peng Chen, Huan Yan, Yong'an Jiang.
      
    Keywords:  DB07993; Microglia; NCAM1; NF-κB; Neuroinflammation; Stroke
    DOI:  https://doi.org/10.1186/s12974-026-03766-7
  7. Acta Neuropathol Commun. 2026 Mar 07.
    microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer's disease patients.
    Amber Penning, Sarah Snoeck, Olmo Ruiz Ormaechea, Dilara Ayyildiz, Oliver Polzer, Martin Buitrago-Arango, Raffaella Capobianco, Fred de Winter, Sriram Balusu, Joost Verhaagen, Carlos P Fitzsimons, Constantin d'Ydewalle, Paul J Lucassen, Dieder Moechars, Lujia Zhou, Evgenia Salta.
      
    Keywords:  Alzheimer’s disease; Microglia; iPSC; miR-132; microRNA
    DOI:  https://doi.org/10.1186/s40478-026-02228-8
  8. Nat Aging. 2026 Mar 10.
    Simultaneous spatial transcriptomics and morphology profiling as tools to explore how microglia change with age.
    Douglas E Henze, Andy P Tsai, Tony Wyss-Coray, Stephen R Quake.
      Cellular morphology is tightly linked to function, but how subcellular transcript localization contributes remains unclear. Using microglia, the brain's resident macrophages, as a model, we combined multiplexed error-robust fluorescence in situ hybridization with immunohistochemistry to map how morphology and subcellular mRNA localization interact with function in young and aged mouse brains. We show that mRNA spatial organization varies across microglial states and defines distinct localization patterns within their processes, revealing morphological heterogeneity within transcriptomically defined populations. Notably, we found a subpopulation of disease-associated-like microglia with a ramified morphology (that is, displaying numerous processes), challenging the conventional assumption between morphology and microglial states. Finally, we found that aging may reshape mRNA distributions and their co-localization networks, shifting microglial programs from intracellular signaling and regulation of phagocytosis toward migration and catabolic regulation. Our findings highlight the role of subcellular transcript organization in shaping microglial morphology and function, offering new avenues for studying and modulating microglial states in health, disease and aging.
    DOI:  https://doi.org/10.1038/s43587-026-01089-z
  9. Nat Commun. 2026 Mar 09.
    Cerebrospinal fluid NPTX1 and NPTXR predict neurodegeneration and clinical progression in Alzheimer's disease.
    Linbin Dai, Bjørn-Eivind Kirsebom, Chenxi Wang, Mengguo Zhang, Qiong Wang, Ming Ni, Fernando Gonzalez-Ortiz, Kaj Blennow, Jiong Shi, Tormod Fladby, Feng Gao, Yong Shen.
      Identifying biomarkers that precisely track the neurodegenerative component of Alzheimer's disease (AD) is essential for effective clinical management. Here we show that cerebrospinal fluid (CSF) levels of the synaptic proteins NPTX1 and NPTXR are robust indicators of disease severity and future clinical progression. In two independent, multi-ethnic cohorts spanning the AD continuum (n = 635), lower CSF NPTX levels correlate strongly with cognitive impairment and cortical thinning in AD-vulnerable regions. Longitudinally, baseline NPTX levels predict accelerated brain atrophy and the clinical transition from mild cognitive impairment to dementia, frequently outperforming or complementing established markers such as pTau181 and neurofilament light chain. These findings establish NPTX1 and NPTXR as sensitive, stage-specific markers of synaptic integrity and neurodegeneration. By accurately forecasting disease progression, these biomarkers offer significant potential to enhance patient stratification and provide a crucial tool for monitoring the efficacy of disease-modifying therapies in clinical trials.
    DOI:  https://doi.org/10.1038/s41467-026-70472-6
  10. J Neuroinflammation. 2026 Mar 11.
    A central role for fibrinogen in promoting microglial repair of the hypoxia-disrupted blood-brain barrier.
    Sebok K Halder, Arjun Sapkota, Richard Milner.
      
    Keywords:  Blood vessels; Blood-brain barrier integrity; Brain; Chronic mild hypoxia; Fibrinogen; Mac-1 integrin; Microglia
    DOI:  https://doi.org/10.1186/s12974-026-03759-6
  11. Elife. 2026 Mar 11. pii: e110753. [Epub ahead of print]15
    Replacing the immune system of the brain.
    Julie Rebejac, Soyon Hong.
      A new method enables engineered immune progenitor cells to replace microglia in mice and reveals how a genetic mutation can lead to inflammation in the brain.
    Keywords:  immunology; inflammation; leukodystrophies; microglia; microglia replacement; mouse; neuroscience; transplantation
    DOI:  https://doi.org/10.7554/eLife.110753
  12. Nat Commun. 2026 Mar 09. pii: 2406. [Epub ahead of print]17(1):
    Multi-modal dissection of cell-type specific TDP-43 pathology in the motor cortex.
    Wolfgang P Ruf, Julia K Kühlwein, Laura Meier, Sarah J Brockmann, Jaehyun LeeBae, Ghazaleh Sadri-Vakili, Deniz Yilmazer-Hanke, Susanne Petri, Dietmar R Thal, Veselin Grozdanov, Karin M Danzer.
      Cytoplasmic TDP-43 pathology is a pathological sign of ALS/ALS-FTD and a converging disease event across different genotypes, phenotypes and CNS areas. To understand this process and target it therapeutically, we need to define which cell types are affected and which cell-type specific effects make them particularly vulnerable. We coupled flow-cytometry nuclear sorting and sequencing with single-nucleus multi-omic ATAC-seq and RNA-seq and spatial transcriptomics to define the transcriptional cell type of affected neurons in the post-mortem ALS/ALS-FTD motor cortex (30 ALS, 20 ALS-FTD & 32 control samples). Here, we show that mainly excitatory cortical neurons are affected by TDP-43 pathology and define the cell types that are affected the most: intratelencephalic L2-L3-LINC00507-FREM3, L3-L5-RORB-LNX2, L3-L5-RORB-ADGRL4 & L6-THEMIS-LINC00343 neurons and extratelencephalic L5-FEZF2-NTNG1 neurons. Transcriptional aberrations by TDP-43 pathology, like cryptic exon inclusion, are cell-type specific and affect distinct gene sets in each cell type, highlighting the need to address TDP-43 pathology in a cell-type specific manner.
    DOI:  https://doi.org/10.1038/s41467-026-69944-6
  13. Proc Natl Acad Sci U S A. 2026 Mar 17. 123(11): e2537058123
    Macrophage-glia interactions regulate immune damage to enteric neurons during West Nile virus infection.
    Hana Janova, Fang R Zhao, Ali Akgul, Meredith Schatz, Daniel M Alligood, David M Alvarado, Larissa B Thackray, Thaddeus S Stappenbeck, Michael S Diamond.
      Functional gastrointestinal (GI) tract disorders affect a substantial proportion of the global population and are often preceded by intestinal infections that cause injury to enteric neurons and glia through unrestrained immune responses. However, the mechanisms that limit infection-induced inflammation and protect the enteric nervous system remain poorly understood. Here, we defined such neuron-glia-macrophage interactions after West Nile virus (WNV) infection; this model neurotropic virus causes GI tract dysmotility in mice via injury of enteric neurons through a T cell-mediated cytolytic mechanism. In response to WNV infection, RNA sequencing analysis showed that resident muscularis macrophages upregulate antiviral, proinflammatory, and immunomodulatory genes. Whereas pharmacological depletion of resident macrophages did not affect the viral burden in the GI tract, it instead reshaped the enteric glial response to WNV, resulting in excessive production of T cell and neutrophil chemoattractants. The amplified recruitment of these immune cell types worsened enteric neuronal injury. Together, our findings identify resident muscularis macrophages as key regulators of glia-driven inflammation during enteric viral infection and reveal their role in protecting enteric neurons from immune-mediated damage.
    Keywords:  gastrointestinal; glia; macrophage; neuron; pathogenesis
    DOI:  https://doi.org/10.1073/pnas.2537058123
  14. Sci Adv. 2026 Mar 13. 12(11): eadz1686
    Persistent microglial activation following neonatal CMV infection mediates neurodegeneration.
    Jessica L McCord, Debotri Chatterjee, John Y S Han, Drew Scoles, Richard J Smeyne, Nancy J Philp, Christopher M Snyder.
      Human cytomegalovirus (HCMV) causes the most common congenital viral infection in the United States, with well-known acute and late-onset neurological pathologies. Moreover, HCMV, like multiple herpesviruses, has been associated with neuroinflammation and neurodegeneration. Using a well-established neonatal murine (M)CMV infection model, we found that early-life infection drove adult-onset neuron loss and neuropathology in the retina and brain, without evident viral reactivation. Pathology was associated with the persistence of highly activated and inflammatory damage-associated microglia. Transient depletion of these microglia before the development of pathology resulted in repopulation of the tissue by microglia with a more reparative profile, which was then sustained over time. Transient microglia depletion alone was sufficient to preserve retinal structure and photoreceptor neurons, promote healing of some existing retinal damage, and preserve brain neuron density in adult infected mice. Thus, early-life infection by MCMV promoted dysfunctional and pathogenic microglia that drove adult-onset neurodegeneration in the eye and brain.
    DOI:  https://doi.org/10.1126/sciadv.adz1686
  15. Nat Med. 2026 Mar 11.
    Blood phosphorylated tau elevation as a biomarker in immunoglobulin light chain and transthyretin amyloidosis.
    Stephan A Kaeser, Stephanie A Schultz, Anna Hofmann, Lisa M Häsler, Ying Xu, Marius Lambert, Ulrike Obermüller, Kathrin Brockmann, Johan Bijzet, Hans Nienhuis, Mario Nuvolone, Laura Obici, Giovanni Palladini, Ute Hegenbart, Stefan O Schönland, Mathias Jucker.
      Elevated blood levels of phosphorylated tau (p-tau) are diagnostic of Alzheimer disease and are associated with the deposition of amyloid-β in the cerebral neuropil. Elevated p-tau levels have also been associated with cerebral deposition of Danish amyloid and prion protein amyloid. Here we analyzed p-tau in serum from four different cohorts of people with the most common types of systemic amyloidosis, transthyretin (ATTR) amyloidosis and immunoglobulin light chain (AL) amyloidosis. We found higher levels of serum p-tau181 in the AL and ATTR groups than in controls. Subsequent analyses revealed that these effects were more pronounced in the presence of polyneuropathy (PNP) and in AL compared to ATTR amyloidosis. Individuals with different forms of PNP that were not due to amyloidosis did not exhibit elevated p-tau181 levels. In cases of presymptomatic (genetic) ATTR, p-tau181 levels increased as a function of predicted years from symptom onset. Additional measurement of p-tau217 in one cohort revealed similar increases, and discriminated people with AL and those with ATTR from controls equally as well as p-tau181. These findings suggest that elevated serum p-tau levels are not specific to Alzheimer disease and may also serve as a diagnostic tool of ATTR and AL amyloidosis, with potential utility in distinguishing amyloidosis-related PNP from PNP of other etiologies.
    DOI:  https://doi.org/10.1038/s41591-026-04272-2
  16. Nat Commun. 2026 Mar 13.
    Microglial cathepsin B is necessary for neuronal efferocytosis in zebrafish and mice during brain development.
    Nicholas J Silva, Sarah R Anderson, Supriya A Mula, Caroline C Escoubas, Haruna Nakajo, Anna V Molofsky.
      Half of all newborn neurons in the developing brain are removed via efferocytosis - the phagocytic clearance of apoptotic cells. Microglia are brain-resident professional phagocytes that play important roles in neural circuit development including as primary effectors of efferocytosis. While the mechanisms through which microglia recognize potential phagocytic cargo are widely studied, the lysosomal mechanisms that are necessary for efficient digestion are less well defined. Here we show that the lysosomal protease cathepsin B is enriched in microglia located in brain regions where neuronal turnover is high in both zebrafish and mouse. Genetic disruption of cathepsin B in zebrafish and mice had an accumulation of microglia containing undigested dead cells. Live imaging studies in zebrafish and in cultured mouse microglia revealed fewer phagocytic events and reduced overall phagocytosis. We also observed behavioral impairments in both models. These data reveal a role for microglial cathepsin B in vertebrate brain development.
    DOI:  https://doi.org/10.1038/s41467-026-70350-1
  17. Nat Commun. 2026 Mar 12.
    Impaired α-Synuclein aggregate clearance in neuronal cells drive their spread to microglia through tunneling nanotubes.
    Ranabir Chakraborty, Francesca Palese, Philippa Samella, Veronica Testa, Jara Montero-Muñoz, Sylvie Syan, Takashi Nonaka, Masato Hasegawa, Antonella Consiglio, Chiara Zurzolo.
      Tunneling nanotubes (TNTs) play a crucial role in intercellular communication, enabling transfer of molecular cargoes over long distances between connected cells. Previous studies have demonstrated efficient, directional transfer of α-Synuclein (α-Syn) aggregates from neurons to microglia, with endosomal trafficking and lysosomal processing identified as the primary events following α-Syn internalization. Using human neuronal and microglial cell lines, we show that microglia exhibit higher lysosomal turnover, particularly through lysophagy, whereas neuronal lysosomes display compromised degradative capacity and impaired autophagic flux upon α-Syn exposure, resulting in compromised aggregate clearance. Such a response to α-Syn aggregates is also conserved in human iPSC-derived neurons and microglia. Moreover, perturbing aggregate clearance via autophagy inhibition enhances TNT-mediated transfer of α-Syn from neuronal cells to microglia. Microglia co-cultured with α-Syn-containing neurons upregulate autophagy flux, enabling efficient degradation of the transferred aggregates. These results highlight dysfunctional autophagy in neurons as a key driver outsourcing α-Syn aggregates to microglia.
    DOI:  https://doi.org/10.1038/s41467-026-69930-y
  18. J Neuroinflammation. 2026 Mar 09.
    Targeting Apolipoprotein E4 rescues photoreceptor degeneration by inhibiting the disease-associated microglia activation in experimental retinal detachment.
    Xiaomeng Li, Niannian Fan, Yuanye Yan, Mingxin Ren, Haomin Wu, Kai Dong.
      
    DOI:  https://doi.org/10.1186/s12974-026-03762-x
  19. EMBO Mol Med. 2026 Mar 10.
    TDP-43 pathology triggers neuroinflammation and cognitive impairment by inducing microglial necroptosis.
    Shenrui Guo, Hongfu Jin, Hui Sun, Shuo Huang, Yuanyuan Chen, Yuge Chang, Yu Zhang, Lin Ding, Suyun Chen, Chenglai Fu, Yafu Yin, Weiwei Cheng.
      Pathological TAR DNA-binding protein-43 (TDP-43) is a defining feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Alzheimer's disease (AD). However, the mechanism by which TDP-43 pathology disrupts microglial function and drives neuroinflammation remains unclear. In this study, we demonstrated that cytoplasmically mis-localized TDP-43 exacerbated neuroinflammation, induced cell death, and impaired phagocytic function in microglial cells, primarily through receptor interacting serine/threonine kinase 3 (RIPK3)-dependent necroptosis. Pharmacological inhibition of RIPK3 with GSK872 markedly attenuated these pathological effects in vitro. These findings were further corroborated in a murine model with cytoplasmic TDP-43 mis-localization, where GSK872 treatment remarkably alleviated neuroinflammation and restored cognitive deficits. Mechanistically, our findings indicate that the nuclear depletion of TDP-43, resulted from its cytoplasmic mis-localization, impairs its ability to transcriptionally repress the Ripk3 gene, subsequently leading to RIPK3 upregulation and activation of RIPK3-dependent necroptosis. Collectively, our findings establish RIPK3-dependent necroptosis as a critical driver of TDP-43 pathology-mediated neuroinflammation and identified necroptosis as a promising therapeutic target in TDP-43-associated neurodegenerative disorders.
    Keywords:  Microglia; Necroptosis; Neuroinflammation; RIPK3; TDP-43
    DOI:  https://doi.org/10.1038/s44321-026-00394-9
  20. Alzheimers Dement. 2026 Mar;22(3): e71229
    Dual association patterns between microglial activation and neuronal health in Alzheimer's disease: a whole-brain MRSI/PET study.
    Yaoyu Zhang, Xiao-Hang Qian, Huixiang Zhuang, Wenqi Zhang, Jialin Hu, Yibo Zhao, Yudu Li, Wen Jin, Chang Xu, Ziyu Meng, Wenli Li, Siyue Chen, Xu-Feng Jiang, Tengfei Guo, Ya-Dong Li, Jian Ye, Zhi-Pei Liang, Biao Li, Miao Zhang, Huidong Tang, Yao Li.
       INTRODUCTION: Microglial activation can either support neuronal function or exacerbate damage, contributing to Alzheimer's disease (AD) progression. We investigated spatial relationships among microglial activation, neuronal health, and amyloid beta (Aβ) in the AD spectrum.
    METHODS: Forty healthy controls, 37 patients with mild cognitive impairment (MCI), and 62 patients with AD underwent whole-brain high-resolution 1H-magnetic resonance spectroscopic imaging (MRSI), [1 8F]DPA-714, and [1 8F]AV-45 positron emission tomography (PET). Regional and voxel-wise analyses assessed changes and associations of microglial activation with N-acetylaspartate (NAA) and Aβ.
    RESULTS: MCI and AD patients showed higher microglial activation and lower NAA, correlating with cognitive decline. In controls and MCI, microglial activation correlated positively with NAA and Aβ in early amyloid-accumulating regions. Conversely, negative correlations with NAA emerged in the hippocampus in MCI and extended to temporal and occipital regions in AD.
    DISCUSSION: For the first time, we identified two distinct spatial association patterns between [1 8F]DPA-714 PET and NAA, shedding light on the complex interplay between neuroinflammation and neuronal health in AD.
    Keywords:  Alzheimer's disease; N‐acetylaspartate; amyloid beta; magnetic resonance spectroscopic imaging; microglial activation; neuroinflammation
    DOI:  https://doi.org/10.1002/alz.71229
  21. J Neuroinflammation. 2026 Mar 07.
    CSF microtubule-associated protein 1 light chain 3A and 3B levels are associated with tau pathology and Alzheimer's disease risk through amyloid deposition and microglial signaling.
    Alzheimer’s Disease Neuroimaging Initiative
      
    Keywords:  Alzheimer’s disease; Amyloid beta-Peptides; Autophagy; Microglia; Tau Proteins
    DOI:  https://doi.org/10.1186/s12974-026-03758-7
  22. J Neuroinflammation. 2026 Mar 12. pii: 85. [Epub ahead of print]23(1):
    CAR T cell therapy in autoantibody-mediated neurological disorders: a promising strategy.
    Muzi Wen, Ruoyi Zheng, Hanqing Zhang, Sophia Y Goldberg, Zhiying Jian, Ye Gao, Ruogu Cheng, Linxin Wen, Yu Zhao, Saad S Kenderian, Pei Shang.
      
    Keywords:  Anti-NMDA receptor encephalitis; Autoantibody-mediated neurological disorders; CAR T cell therapy; Diacylglycerol lipase alpha antibody associated encephalitis; Lambert-Eaton myasthenic syndrome; MOG antibody-associated disease; Multiple sclerosis; Myasthenia gravis; Neuromyelitis optica spectrum disorder; Stiff person syndrome
    DOI:  https://doi.org/10.1186/s12974-025-03662-6
  23. FASEB J. 2026 Mar 31. 40(6): e71631
    Extracellular Vesicles Secreted by Human Microglia Support Blood-Brain Barrier Function Under Both Physiological and Inflammatory Conditions.
    Agnė Pociūtė, Kotryna Milovanovaitė, Agnė Jokubauskytė, Augustas Pivoriūnas.
      Brain endothelial cells (BECs) are essential for maintaining central nervous system homeostasis through the formation of the blood-brain barrier (BBB), whose integrity depends on continuous signaling from neighboring cells of the neurogliovascular unit. Although microglia are positioned in close proximity to cerebral vessels, their contribution to BBB regulation remains poorly defined. Here, we investigated the impact of paracrine signals from human microglia on BBB function under homeostatic and inflammatory conditions. Using a non-contact co-culture system with human induced pluripotent stem cell-derived BECs, we found that unstimulated microglia enhanced BBB integrity, as evidenced by increased transendothelial electrical resistance (TEER), upregulation of the tight junction proteins claudin-5, occludin, and ZO-1, and promotion of BEC proliferation. In contrast, TNFα-activated microglia did not support barrier integrity. Conditioned media from unstimulated microglia recapitulated the TEER-enhancing effects, whereas extracellular vesicle (EV)-depleted conditioned media failed to do so, implicating EVs as key mediators. Purified EVs from both unstimulated and TNFα-activated microglia promoted proliferation, increased TEER, elevated tight junction protein expression, and, notably, mitigated TNFα-induced barrier disruption by preserving TEER, endothelial proliferation, and tight junction continuity. Together, these findings identify microglia-derived EVs as potent positive regulators of BBB integrity and demonstrate that, even under inflammatory activation, microglial EVs retain the capacity to support endothelial barrier function. This work reveals a previously underappreciated mechanism by which microglia contribute to vascular homeostasis and suggests microglial EVs as potential therapeutic targets for preserving BBB integrity in neuroinflammatory diseases.
    Keywords:  blood–brain barrier; extracellular vesicles; microglia; tight junctions; transendothelial electrical resistance
    DOI:  https://doi.org/10.1096/fj.202504928R
  24. Cell Metab. 2026 Mar 10. pii: S1550-4131(26)00051-3. [Epub ahead of print]
    Immune cells regulate circulating adipocyte extracellular vesicle levels in response to metabolic shifts.
    Snigdha Tiash, Saket Awadhesbhai Patel, Marjori Russo, Anusha Suresh, Bo Pang, Yun-Ling Pai, Wentong Jia, Rachael L Field, Terri Pietka, Nada A Abumrad, Gordon I Smith, Dmitri Samovski, Samuel Klein, Jonathan R Brestoff, Clair Crewe.
      Extracellular vesicles (EVs) are now recognized as potent mediators of inter-organ signaling and are implicated in the pathogenesis of obesity and associated comorbidities. Despite a recent surge in functional information about EVs, we still lack a basic understanding of how endogenous EV levels are controlled to regulate inter-organ signaling. New flow cytometry technologies have allowed us to study the regulation of circulating endogenous EVs from metabolically relevant cell types such as adipocytes (adipocyte-derived EVs [adipoEVs]). We provide evidence for a paradigm of EV regulation in which tissue-resident immune cells, predominantly macrophages, clear EVs released by local tissue cells or those entering the tissue from circulation, an activity that determines circulating EV levels. In obesity, EV uptake by adipose tissue immune cells is reduced, leading to increased circulating adipoEVs and reduced adipoEV clearance rates. This work shows that tissue immune cells gate tissue EV entry into the circulation, making them key regulators of inter-organ EV signaling.
    Keywords:  adipocyte; exosomes; extracellular vesicles; insulin resistance; inter-organ signaling; macrophage; mitochondria; obesity; spectral flow cytometry; type 2 diabetes
    DOI:  https://doi.org/10.1016/j.cmet.2026.02.008
  25. Alzheimers Dement. 2026 Mar;22(3): e71249
    The neuromodulatory fragility hypothesis of Alzheimer's disease pathogenesis.
    Alfie Wearn, Kate M Onuska, Taylor W Schmitz, Gary R Turner, R Nathan Spreng.
      Sporadic Alzheimer's disease (AD) is associated with numerous risk factors, yet its precise cause remains unclear. Here, we describe a novel framework for AD pathogenesis, whereby diverse risk factors converge on neuromodulatory subcortical systems to confer AD risk or resilience. Neuromodulatory projection neurons are uniquely fragile due to their large size, sparse myelination, and high basal metabolic demands. We propose that the increased prevalence of AD in older adult populations likely reflects a universal weakness within these projection systems, which is increasingly exposed as cellular transport and maintenance mechanisms deteriorate with age. The key insight of this "neuromodulatory fragility hypothesis" is that neuromodulatory system dysfunction is sufficient to explain both tau hyperphosphorylation and amyloid beta plaque formation, the two pathological hallmarks of AD. We therefore predict that strengthening or preserving the endogenous functions of these systems in midlife represents the most effective strategy for preventing AD.
    Keywords:  Alzheimer's disease; acetylcholine; amyloid beta; dopamine; neuroinflammation; neuromodulatory subcortical systems; neuronal resilience; neuronal vulnerability; noradrenaline; orexin; pathogenesis; risk factors; serotonin; tau
    DOI:  https://doi.org/10.1002/alz.71249
  26. J Neuroinflammation. 2026 Mar 14.
    Tumor immunogenicity shapes CNS immune niches and CD8⁺ T cell fate in glioblastoma.
    Suman Asalla, Omar Santiagonunez Ahumada, Jordan E Krull, Yan Wang, Disha N Patel, Vivaan Gupta, Andreas Wieland, Pierre Giglio, Qin Ma, Andrea Tedeschi, Benjamin M Segal, Nandini Acharya.
      
    DOI:  https://doi.org/10.1186/s12974-026-03754-x
  27. Nat Commun. 2026 Mar 07. pii: 2318. [Epub ahead of print]17(1):
    A human cerebral organoid model of West Nile virus encephalitis shows innate immunocompetency.
    Johanna Friederike Steffen, Lina Widerspick, Stephanie Jansen, Dennis Tappe.
      West Nile virus (WNV), an arbovirus of emerging global interest, can cause neuroinvasive disease in humans. Currently, no protective vaccine or specific treatment is available for human WNV encephalitis. The virus induces neuronal cell death, while astrocytes and microglia cells are suspected to contribute to WNV pathology. Hence, understanding their role is crucial for future treatment approaches. In this study, we establish a WNV encephalitis model using human cerebral organoids, generated with male iPSCs. Infection results in heterogeneous kinetics with an early strong replication potentially leading to viral clearance, while a late peak was associated with more long-term infection. Viral foci are seen in cortical-like areas, rich in neurons and astrocytes, however void of microglia. Pro-inflammatory cytokines (IL-6, TNF-α, IL-18), chemokines (CXCL10, CCL17, CX3CL1, CCL2) and biomarkers (IL-1RA, sTREM-1, sRAGE, BDNF) are increasingly released. Conclusively, human cerebral organoids make suitable WNV encephalitis models with valuable properties to study acute and long-term infection.
    DOI:  https://doi.org/10.1038/s41467-026-70281-x
  28. Mol Neurobiol. 2026 Mar 14. pii: 498. [Epub ahead of print]63(1):
    The Interferon-miR-146a-5p-Stat1/Nrf2 Pathway Mediates LRRK2-R1441G-induced M1 over M2 Microglia Activation.
    Lishan Lin, Junfeng Luo, Xiantao Wang, Tanvikhaa Saravanan, Gabriela Mercado, Yucheng Li, Ya Zhang, Liliana D Florea, Markus Hafner, Zhong Pei, Wanli W Smith.
      Parkinson's disease (PD) is the second most common neurodegenerative disease with movement disorder. The etiology and molecular pathogenesis of PD are not fully understood. Mutations in the LRRK2 gene are the primary genetic causes of PD and contribute to sporadic PD. Mitochondrial dysfunction and neuroinflammation have been reported in LRRK2-based PD models. However, the molecular mechanisms in LRRK2-linked PD remain largely unknown. In this study, we used a human microglial cell line (HMC-3) to study the effects of mutant LRRK2-R1441G and a mitochondrial toxin (MPP+), on microglial activation and its linked gene and pathway changes using RNA sequencing combined with biological assays. We found that mutant LRRK2-R1441G with MPP+ exposure induced M1 rather than M2 microglial activation by activating the interferon signaling pathway and reducing miR-146a-5p function thereby elevating its targeted genes, such as Stat1, and reducing Nrf2 levels to inhibit neuroinflammation. Whereas treatment of LRRK2 kinase inhibitor or elevated miR-146a-5p could promote the shift of microglia from M1 to M2 activation by correcting interferon signaling and/or restoring the miR-146a-5p levels, reducing Stat1 and increasing Nrf2 levels thereby inhibiting neuroinflammation. Our findings not only provide novel insights into the mechanisms of LRRK2 regulating microglial activation underlying neuroinflammation in PD pathogenesis but also validate that targeting LRRK2 and/or miR-146a-5p could be potential novel treatment strategies for PD and other LRRK2-linked neuroinflammatory disorders.
    Keywords:  LRRK2; MiRNA; Microglia activation; Neuroinflammation; Nrf2; Stat1
    DOI:  https://doi.org/10.1007/s12035-026-05762-7
  29. J Neurosci. 2026 Mar 12. pii: e0011252026. [Epub ahead of print]
    Motoneurons inhibitory synapses homeostatically respond to neuronal activity and modulate Amyotrophic Lateral Sclerosis pathogenesis.
    Kareen Halablab, Gizem Yartas, Natalie Dikwella, Oumayma Aousji, Burak Ozkan, Cedric Jan, Diana Wiesner, Simon M Danner, Guillaume Caron, Daniel Zytnicki, Francesco Roselli.
      Alterations in Excitation/inhibition (E/I) balance and changes in motor neurons (MN) activity may contribute to MN vulnerability in ALS. The balance of pathogenic vs adaptive changes occurring in inhibitory synapses and affecting E/I balance remain unclear. Confocal microscopy of MN from P45 male SOD1G93A mice reveal downregulated GlyR but upregulated GABAR clusters at inhibitory synapses. GlyR and GABAR respond to PSAM and DREADD chemogenetic alterations of MN excitability, with increased activity driving increase in inhibitory clusters. An E3 ligase-conjugated intrabody (GFE3) degrades Gephyrin, decreases GABAR and GlyR clusters, increases net activity and downregulates disease markers. However, simultaneous decrease of inhibition and increased activity by actPSAM and GFE3 shows no net beneficial effects on disease markers. Thus inhibitory synapses are involved in the early phases of ALS pathogenesis and respond to persistent homeostatic loops and their suppression delivers a net activity increase, offering potential benefits on disease pathways.Significance Statement This study reveals significant changes in inhibitory connections onto motor neurons (MN) during the early stages of ALS, highlighting their involvement in the excitation/inhibition (E/I) imbalance seen at this disease stage. Using advanced chemogenetic tools, we show that inhibitory synapses respond homeostatically to modulations in MN activity. Moreover, decreasing inhibitory receptor components using a functionalized nanobody increases net MN excitability and reduces disease markers. These findings show the dynamic nature of inhibitory synapses in ALS MN, emphasizing their abilities to adapt to activity changes which can in turn influence disease progression.
    DOI:  https://doi.org/10.1523/JNEUROSCI.0011-25.2026
  30. Nutrients. 2026 Feb 26. pii: 749. [Epub ahead of print]18(5):
    Polyunsaturated Fatty Acid Balance Modulates Microglial State in a Murine Model of Oxygen-Induced Neovascularization.
    Esther S Kim, Meng-Chin Lin, Cheng-Hsiang Lu, David Casero, Brian Aguirre, Joanne Brown, Olawande Olagoke, Camilia R Martin, Madhuri Wadehra, Kara L Calkins, Alison Chu.
      Background/Objectives: The retina is enriched in polyunsaturated fatty acids (PUFAs) which are indispensable for normal vision, and recent clinical studies have shown that dietary supplementation of ω-6-and ω-3-polyunsaturated fatty acids (PUFAs) can provide a protective role against retinopathy of prematurity (ROP). Our study aims to understand the mechanisms by which altering ω-6-and ω-3-polyunsaturated fatty acids (PUFAs) in the eye can protect against pathologic retinal neovascularization (NV). Methods: We interrogated the effects of endogenous ω-3-PUFA enrichment using transgenic fat-1 mice which convert ω-6-PUFAs to ω-3-PUFAs in the oxygen-induced retinopathy (OIR) murine model. In the OIR model, mice are exposed to 75% oxygen from postnatal day 7 (P7) to P12, then returned to room air (RA). We used a combination of immunofluorescence, bulk retinal RNA sequencing, and lipid mediator profiling by UHPLC-MS/MS in P17 mouse retinas to identify mechanisms underlying the protective effect against NV seen in fat-1 mice exposed to OIR. Results:Fat-1 OIR mice were protected against the development of retinopathy, demonstrating 15.1% less vaso-obliteration (75.5% relative reduction) after OIR and a 6.1% reduction in neovascularization (71.8% relative reduction) at P17 (p < 0.0001 for both). We found a dampened transcriptional response to OIR in the retina of fat-1 mice as compared to WT mouse retinas (198 vs. 782 genes, adjusted p-value < 0.01). Pathway analyses confirmed these findings, with significant OIR-induced transcriptional shifts in angiogenesis (adjusted p-value < 10-27), inflammation (adjusted p-value < 10-25), and microglial activation pathways (adjusted p-value < 10-9) in WT mouse retina that were not observed in fat-1 mice. Enrichment scores obtained through the integration of our bulk transcriptomics data with cell-resolved retina data indicate that the protective phenotype observed in fat-1 mice could be associated with intrinsic differences in microglia cell subtypes between WT and fat-1 mice. In situ, WT OIR mice demonstrated an increase in Iba1+ microglia compared to WT RA mice, whereas fat-1 OIR mice showed no difference when compared to fat-1 RA mice. Three ARA-derived oxylipins, 12-hydroxyeicosatetraenoic acid (12-HETE), prostaglandin D2 (PGD2), and thromboxane B2 (TXB2) demonstrated a pattern of upregulation in WT OIR compared to WT RA, but no upregulation in fat-1 OIR mice compared to fat-1 RA. Two EPA-derived specialized pro-resolving mediators and two LA-derived oxylipins were also differentially expressed. Conclusions: These findings show that a lower ω-6:ω-3 protects against neovascularization and is associated with attenuation of hyperoxia-induced microglial recruitment and activation, as well as inflammation and angiogenic signaling.
    Keywords:  angiogenesis; hypoxia; microglia; oxygen-induced retinopathy; polyunsaturated fatty acids; retina; retinopathy of prematurity
    DOI:  https://doi.org/10.3390/nu18050749
  31. J Neuroinflammation. 2026 Mar 12.
    Immune imbalance between T helper 1, T helper 17 and regulatory T cells fuels amyotrophic lateral sclerosis pathogenesis: disease trajectory, diagnosis and therapeutic implications.
    Chloe Sligar, Ronald Sluyter, Lezanne Ooi.
      
    Keywords:  Immune regulation; Microglia; Motor neuron disease; Neuroinflammation; T cell
    DOI:  https://doi.org/10.1186/s12974-026-03764-9
  32. Proc Natl Acad Sci U S A. 2026 Mar 17. 123(11): e2528913123
    Sleep deprivation exhibits an age-dependent effect on infraslow global brain activity.
    Yibing Yang, Weiwei Zhao, Yutong Mao, Tianxin Mao, Yao Deng, Yifan Yang, Hengyi Rao, Xiao Liu.
      Infraslow (<0.1 Hz) global brain activity, quantified by the global mean blood-oxygenation-level-dependent (gBOLD) signal in resting-state functional magnetic resonance imaging (fMRI), is elevated during sleep and coupled to cerebrospinal fluid (CSF) dynamics, a key pathway for the brain waste clearance implicated in neurodegenerative disorders such as Alzheimer's disease. However, the effect of sleep deprivation on gBOLD activity and its interaction with aging remain poorly understood. Using a rigorously controlled in-laboratory total sleep deprivation (TSD) protocol, we demonstrate that TSD significantly increases both the gBOLD signal amplitude and its coupling with CSF flow, suggesting a compensatory mechanism that may enhance glymphatic clearance following acute sleep loss. Notably, these TSD-induced enhancements exhibit robust age dependency, with markedly attenuated responses in midlife adults (40 to 50 y). The absence of this compensatory mechanism in midlife may exacerbate age-related impairments in neurotoxic clearance and increase dementia susceptibility, thereby offering mechanistic insights into the nexus between sleep disruption, aging, and neurodegeneration.
    Keywords:  cerebrospinal fluid; global brain activity; sleep deprivation
    DOI:  https://doi.org/10.1073/pnas.2528913123
  33. Mol Neurobiol. 2026 Mar 11. pii: 493. [Epub ahead of print]63(1):
    Amyloid-β and Mitochondrial Membranes: A Missing Link in Alzheimer's Pathogenesis.
    Aneta Houfkova, Monika Schmidt.
      Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by memory loss and cognitive decline, predominantly in the elderly (Alzheimer Disease International et al., 2015). Although amyloid-β peptide (Aβ), particularly in its oligomeric forms, has long been linked to AD pathogenesis (Chen 9:1205-1235 2017, Gaspar 2 394-400 2010), the mechanisms underlying its cellular toxicity remain unclear. Mitochondrial dysfunction is a consistent feature of AD (D'Alessandro 107:102713 2025), yet how Aβ drives these alterations is not fully understood. This review integrates recent evidence showing that Aβ accumulates on mitochondrial membranes (Cenini 21:3257-3272 2016, Manczak 23:5131-5146 2006, Sirk 5:1989-2003 2007), providing a mechanistic link between amyloid pathology and mitochondrial damage. We discuss how membrane-associated Aβ disrupts mitochondrial protein import by impairing the translocase of the outer membrane (TOM) complex (Cenini 21:3257-3272 2016, Sirk 5:1989-2003 2007) and interferes with voltage-dependent anion channel 1 (VDAC1) (Smilansky 52:30670-30683 2015), a key regulator of metabolite exchange and apoptosis. We further emphasize the role of mitochondria-associated membranes (MAMs) as critical sites for Aβ generation and transfer to mitochondria, where dysregulated cholesterol metabolism may amplify MAM activity and Aβ accumulation (Area-Gomez and Schon 38:90-96 2017, Monaghan 2:240287 2025). Altogether, we propose that mitochondrial membrane localization of Aβ is a central mechanism linking amyloid pathology to mitochondrial dysfunction in aging, highlighting new directions for mitochondria-targeted therapeutic strategies in AD.
    Keywords:  Amyloid-β; Cholesterol; Mitochondria; Mitochondria-associated membranes; Proteostasis; Translocase of outer membrane; Voltage-dependent anion channel
    DOI:  https://doi.org/10.1007/s12035-026-05786-z
This page is being maintained by Thomas Krichel. It was last updated on 2026‒03‒23 at 0:10.