bims-proned 2025-04-20 papers

bims-proned

Biomed News

on Proteostasis in neurodegeneration

Issue of 2025–04–20
thirteen papers selected by
Verena Kohler, Umeå University

The role of phospholipid saturation and composition in α-synuclein aggregation and toxicity: A dual in vitro and in vivo approach.
Aggregation of α-synuclein splice isoforms through a phase separation pathway.
Optogenetic induction of TDP-43 aggregation impairs neuronal integrity and behavior in Caenorhabditis elegans.
Unravelling the Proteinopathic Engagement of α-Synuclein, Tau, and Amyloid Beta in Parkinson's Disease: Mitochondrial Collapse as a Pivotal Driver of Neurodegeneration.
Inhibitor-based modulation of huntingtin aggregation mechanisms mitigates fibril-induced cellular stress.
Osthole's capacity to prevent tau aggregation, a key protein in tauopathy and Alzheimer's disease.
Single-molecule observations of human small heat shock proteins in complex with aggregation-prone client proteins.
Identification of novel small molecule chaperone activators for neurodegenerative disease treatment.
A ROS-Responsive nanoparticle for nuclear gene delivery and autophagy restoration in Parkinson's disease therapy.
Early A-synuclein aggregation decreases corticostriatal glutamate drive and synapse density.
Lysosomal Dysfunction in Amyotrophic Lateral Sclerosis: A Familial Case Linked to the p.G376D TARDBP Mutation.
4-Amino-3',4'-dihydroxychalcone Increases Tau Dynamics in Phase-Separated Droplets and Inhibits Tau Aggregation.
The potential of erythrocyte α-synuclein to differentiate dementia with Lewy bodies from Parkinson's and Alzheimer's diseases.

Protein Sci. 2025 May;34(5): e70121

The role of phospholipid saturation and composition in α-synuclein aggregation and toxicity: A dual in vitro and in vivo approach.

Aidan P Holman, Tianyi Dou, Mikhail Matveyenka, Kiryl Zhaliazka, Anjni Patel, Avery Maalouf, Ragd Elsaigh, Dmitry Kurouski.

  Parkinson's disease is characterized by a progressive accumulation of α-synuclein (α-syn) aggregates in Lewy bodies, extracellular deposits found in the midbrain, hypothalamus, and thalamus. The rate of α-syn aggregation, as well as the secondary structure of α-syn oligomers and fibrils, can be uniquely altered by lipids. However, the role of saturation of fatty acids (FAs) in such lipids in the aggregation properties of α-syn remains unclear. In this study, we investigated the effect of saturation of FAs in phosphatidylcholine (PC) and cardiolipin (CL), as well as a mixture of these phospholipids on the rate of α-syn aggregation. We found that although saturation plays very little if any role in the rate of protein aggregation and morphology of α-syn aggregates, it determined the secondary structure of α-syn oligomers and fibrils. Furthermore, we found that aggregates formed in the presence of both saturated and unsaturated PC and CL, as well as mixtures of these phospholipids, exert significantly higher cell toxicity compared to the protein aggregates formed in the lipid-free environment. To extend these findings, we conducted in vivo studies using C. elegans, where we assessed the effect of lipid-modified α-syn aggregates on organismal survival and neurotoxicity. Our results suggest that the saturation of FAs in phospholipids present in the plasma and mitochondrial membranes can be a key determinant of the secondary structure and, consequently, the toxicity of α-syn oligomers and fibrils. These findings provide new insights into the role of lipids in Parkinson's disease pathogenesis and highlight potential targets for therapeutic intervention.

Keywords:  AFM‐IR; alpha‐synuclein; amyloids; lipids; oligomers

DOI:  https://doi.org/10.1002/pro.70121
Sci Adv. 2025 Apr 18. 11(16): eadq5396

Aggregation of α-synuclein splice isoforms through a phase separation pathway.

Alexander Röntgen, Zenon Toprakcioglu, Samuel T Dada, Owen M Morris, Tuomas P J Knowles, Michele Vendruscolo.

The aggregation of α-synuclein (αSyn) is associated with Parkinson's disease and other related synucleinopathies. Considerable efforts have thus been directed at understanding this process. However, the recently discovered condensation pathway, which involves the formation of phase-separated liquid intermediate states, has added further complexity. In parallel, it has been reported that different αSyn splice isoforms may be implicated in aggregate formation in disease. In this study, we compare the phase behavior of four αSyn isoforms (αSyn-140, αSyn-126, αSyn-112, and αSyn-98). Using different biophysical tools including confocal microscopy, kinetic assays and microfluidic-based approaches, we find stark differences between the four systems in their propensities to undergo phase separation and aggregation. Furthermore, we show that even small amounts of αSyn-112, one of the predominant isoforms after αSyn-140, can affect the phase separation of αSyn-140. These results highlight the importance of conducting further investigations to elucidate the role of alternative splicing in synucleinopathies.

DOI: https://doi.org/10.1126/sciadv.adq5396
Transl Neurodegener. 2025 Apr 16. 14(1): 20

Optogenetic induction of TDP-43 aggregation impairs neuronal integrity and behavior in Caenorhabditis elegans.

Kyung Hwan Park, Euihyeon Yu, Sooji Choi, Sangyeong Kim, Chanbin Park, J Eugene Lee, Kyung Won Kim.

   BACKGROUND: Cytoplasmic aggregation of TAR DNA binding protein 43 (TDP-43) in neurons is one of the hallmarks of TDP-43 proteinopathy. Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are closely associated with TDP-43 proteinopathy; however, it remains uncertain whether TDP-43 aggregation initiates the pathology or is a consequence of it.
METHODS: To demonstrate the pathology of TDP-43 aggregation, we applied the optoDroplet technique in Caenorhabditis elegans (C. elegans), which allows spatiotemporal modulation of TDP-43 phase separation and assembly.
RESULTS: We demonstrate that optogenetically induced TDP-43 aggregates exhibited insolubility similar to that observed in TDP-43 proteinopathy. These aggregates increased the severity of neurodegeneration, particularly in GABAergic motor neurons, and exacerbated sensorimotor dysfunction in C. elegans.
CONCLUSIONS: We present an optogenetic C. elegans model of TDP-43 proteinopathy that provides insight into the neuropathological mechanisms of TDP-43 aggregates. Our model serves as a promising tool for identifying therapeutic targets for TDP-43 proteinopathy.

Keywords:   C. elegans ; Amyotrophic lateral sclerosis; Frontotemporal lobar degeneration; Neurodegenerative diseases; OptoDroplet; Optogenetics; TDP-43 proteinopathy

DOI:  https://doi.org/10.1186/s40035-025-00480-x
Neurochem Res. 2025 Apr 16. 50(3): 145

Unravelling the Proteinopathic Engagement of α-Synuclein, Tau, and Amyloid Beta in Parkinson's Disease: Mitochondrial Collapse as a Pivotal Driver of Neurodegeneration.

Tarini Ashish Sahoo, Jagdish Chand, Amarjith Thiyyar Kandy, Shanish Antony, Gomathy Subramanian.

  Parkinson's disease is a complex neurological ailment manifested by dopaminergic neurodegeneration in the substantia nigra of the brain. This study investigates the molecular tripartite interaction between Lewy bodies, amyloid beta, and tau protein in the pathogenesis of Parkinson's disease. Lewy bodies which have been found as the important pathological hallmark in the degenerative neurons of Parkinson's patients, are mainly composed of α-synuclein. The accumulation of α-synuclein has been directly and indirectly linked to the severity and degree of progression of the disease. In addition, approximately 50% of Parkinson's disease cases are also described by hyperphosphorylation of tau protein indicating its significant involvement in the disease. The study further explains how α-synuclein, tau and amyloid beta can spread via cross-seeding mechanisms and accelerate each other's aggregation leading to neuronal death. Both GSK-3β and CDK5 are involved in phosphorylation which among other effects contributes to the misfolding of both α-synuclein and tau proteins that lead to neurodegeneration in Alzheimer's disease. Several mediators, that contribute to mitochondrial damage through elevated oxidative stress pathology are clearly described. Because of the increase in the incidence of Parkinson's disease, as predicted to be 17 million when the study was being conducted, studying these pathological mechanisms is very important in trying to establish treatments. This work contributes a path to finding a multi-target treatment regimen to alleviate the burden of this devastating disease.

Keywords:  Amyloid beta; GSK-3β. CDK5; Lewy bodies; Tau protein

DOI:  https://doi.org/10.1007/s11064-025-04399-7
Nat Commun. 2025 Apr 15. 16(1): 3588

Inhibitor-based modulation of huntingtin aggregation mechanisms mitigates fibril-induced cellular stress.

Greeshma Jain, Marina Trombetta-Lima, Irina Matlahov, Hennrique Taborda Ribas, Tingting Chen, Raffaella Parlato, Giuseppe Portale, Amalia M Dolga, Patrick C A van der Wel.

Huntington's disease (HD) is a neurodegenerative disorder in which mutated fragments of the huntingtin protein (Htt) undergo misfolding and aggregation. Since aggregated proteins can cause cellular stress and cytotoxicity, there is an interest in the development of small molecule aggregation inhibitors as potential modulators of HD pathogenesis. Here, we study how a polyphenol modulates the aggregation mechanism of huntingtin exon 1 (HttEx1) even at sub-stoichiometric ratios. Sub-stoichiometric amounts of curcumin impacted the primary and/or secondary nucleation events, extending the pre-aggregation lag phase. Remarkably, the disrupted aggregation process changed both the aggregate structure and its cell metabolic properties. When administered to neuronal cells, the 'break-through' protein aggregates induced significantly reduced cellular stress compared to aggregates formed in absence of inhibitors. Structural analysis by electron microscopy, small angle X-ray scattering (SAXS), and solid-state NMR spectroscopy identified changes in the fibril structures, probing the flanking domains in the fuzzy coat and the fibril core. We propose that changes in the latter relate to the presence or absence of polyglutamine (polyQ) β-hairpin structures. Our findings highlight multifaceted consequences of small molecule inhibitors that modulate the protein misfolding landscape, with potential implications for treatment strategies in HD and other amyloid disorders.

DOI: https://doi.org/10.1038/s41467-025-58691-9
Int J Biol Macromol. 2025 Apr 15. pii: S0141-8130(25)03787-0. [Epub ahead of print] 143235

Osthole's capacity to prevent tau aggregation, a key protein in tauopathy and Alzheimer's disease.

Weiwei Liu, Hui Xu, Chen Wang, Geng Geng, Yuying Yang, Guofang Chen.

  Aggregated forms of protein arising from misfolded variants under physiological conditions can lead to the development of disorders related to proteinopathy, including Alzheimer's disease (AD). Some small molecules derived from plants can enhance the process of protein disaggregation via various pathways. Among the different bioactive substances, osthole-a natural coumarin compound-can be highly effective against protein aggregation and associated proteinopathies. In this research, we investigated osthole's capacity to prevent tau aggregation, a key protein in tauopathy and AD. Osthole was discovered to impede amyloid fibril formation by modulating the kinetics of fibril assembly. In addition, osthole has the potential to enhance the α-helix percentage of tau, while the fractions of β-sheet and random coil were reduced, suggesting that osthole can proficiently stabilize tau structure. Osthole hindered the structural shift from random coil to β-sheet and the creation of hydrophobic areas. Fluorescence spectroscopy and docking analysis indicated that nonpolar and intermolecular energies play a greater role in forming the osthole-tau complex than polar energy, and hydrophobic residues LEU344, ILE354, and PHE346 participating in the strong interaction (logKb values ranging from 5.09 to 5.41 across the studied temperature range). Osthole effectively reduced amyloid-induced neurotoxicity in SH-SY5Y cells by inhibiting ROS production and caspase-3 mRNA expression and activity. In summary, we suggest that osthole could serve as a small molecule for treating different tauopathy-related disorders, justifying additional research moving forward.

Keywords:  Aggregation; Osthole; Tau fibrillation

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.143235
Biochem J. 2025 Apr 09. pii: BCJ20240473. [Epub ahead of print]

Single-molecule observations of human small heat shock proteins in complex with aggregation-prone client proteins.

Lauren Rice, Nicholas Marzano, Dezerae Cox, Bailey Skewes, Antoine van Oijen, Heath Ecroyd.

  Small heat shock proteins (sHsps) are molecular chaperones that act to prevent the aberrant aggregation of misfolded proteins. Whilst it is suggested that sHsps prevent aggregation by binding to misfolded client proteins, the dynamic and heterogeneous nature of sHsps has hindered attempts to establish the mechanistic details of how sHsp-client protein complexes form. Single-molecule approaches have emerged as a powerful tool to investigate dynamic and heterogeneous interactions such as those that can occur between sHsps and their client proteins. Here, we use total internal reflection fluorescence microscopy to observe and characterise the complexes formed between model aggregation-prone client proteins [firefly luciferase (FLUC), rhodanese, and chloride intracellular channel 1 protein (CLIC)], and the human sHsps αB-crystallin (αB-c; HSPB5) and Hsp27 (HSPB1). We show that small (monomeric or dimeric) forms of both αB-c and Hsp27 bind to misfolded or oligomeric forms of the client proteins at early stages of aggregation, resulting in the formation of soluble sHsp-client complexes. Stoichiometric analysis of these complexes revealed that additional αB-c subunits accumulate onto pre-existing sHsp-client complexes to form larger species - this does not occur to the same extent for Hsp27. Instead, Hsp27-client interactions tend to be more transient than those of αB-c. Elucidating these mechanisms of sHsp function is crucial to our understanding of how these molecular chaperones act to inhibit protein aggregation and maintain cellular proteostasis.

Keywords:  Hsp27; molecular chaperones; photobleaching; proteostasis; single-molecule fluorescence; αB-crystallin

DOI:  https://doi.org/10.1042/BCJ20240473
Biomed Pharmacother. 2025 Apr 15. pii: S0753-3322(25)00243-4. [Epub ahead of print]187 118049

Identification of novel small molecule chaperone activators for neurodegenerative disease treatment.

Anita K Ho, Fiona Jeganathan, Magda Bictash, Han-Jou Chen.

  A pathological hallmark of neurodegenerative disease is the accumulation of aberrant protein aggregates which contribute to the cytotoxicity and are therefore a target for therapy development. One key mechanism to manage cellular protein homeostasis is heat shock proteins (HSPs), protein chaperones which are known to target aberrant protein accumulation. Activation of HSPs target aberrant TDP-43, tau and amyloid to rescue neurodegenerative disease. As an attempt to target HSP activation for neurodegeneration therapy, we here develop a drug screening assay to identify compounds that will activate the master regulator of HSPs, the transcription factor heat shock factor 1 (HSF1). As HSF1 is bound by HSP90 which prevents its activation, we developed a NanoBRET assay, which allows us to monitor and quantify the HSF1-HSP90 interaction in living cells to screen for compounds disrupting this interaction and thereby releasing HSF1 for activation. After the optimisation and validation of the assay, a two thousand compound library was screened which produced 10 hits including two known HSP90 inhibitors. Follow-up functional study showed that one of the hits oxyphenbutazone (OPB) significantly reduces the accumulation of insoluble TDP-43 in a cell model, eliciting no signs of stress or toxicity. Overall, this study demonstrates a viable strategy for new drug discovery in targeting aberrant proteins and identifies potential candidates for translation into neurodegenerative disease treatment.

Keywords:  Chaperones; Drug screening; HSF1; Neurodegenerative disease; TDP-43

DOI:  https://doi.org/10.1016/j.biopha.2025.118049
Biomaterials. 2025 Apr 15. pii: S0142-9612(25)00264-9. [Epub ahead of print]321 123345

A ROS-Responsive nanoparticle for nuclear gene delivery and autophagy restoration in Parkinson's disease therapy.

Limin Zhai, Yifei Gao, Hao Yang, Haoyuan Wang, Beining Liao, Yuxue Cheng, Chao Liu, Jingfeng Che, Kunwen Xia, Lingkun Zhang, Yanqing Guan.

  Parkinson's disease (PD) is characterized by the pathological aggregation of α-synuclein (α-syn) and neuroinflammation. Current gene therapies face challenges in nuclear delivery and resolving pre-existing α-syn aggregates. Here, we developed glucose-and trehalose-functionalized carbonized polymer dots (GT-PCDs) loaded with plasmid DNA (pDNA) for targeted gene delivery and autophagy restoration. The GT-PCDs@pDNA nanoparticles exhibit reactive oxygen species (ROS)-responsive behavior, enabling efficient nuclear entry under oxidative stress conditions. Both in vitro and in vivo studies demonstrated that GT-PCDs@pDNA effectively silenced SNCA gene expression, reduced α-syn aggregates, and restored autophagic flux by promoting transcription factor EB (TFEB) nuclear translocation. Moreover, GT-PCDs@pDNA enhanced blood-brain barrier (BBB) permeability via glucose transporter 1 (Glut-1)-mediated transcytosis, significantly improving motor deficits and reducing neuroinflammation in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. This multifunctional nanocarrier system offers a promising strategy for combined gene therapy and autophagy modulation in neurodegenerative diseases.

Keywords:  Autophagy; Nuclear gene delivery; Parkinson's disease; ROS response; α-synuclein

DOI:  https://doi.org/10.1016/j.biomaterials.2025.123345
Neurobiol Dis. 2025 Apr 16. pii: S0969-9961(25)00134-2. [Epub ahead of print] 106918

Early A-synuclein aggregation decreases corticostriatal glutamate drive and synapse density.

Charlotte F Brzozowski, Harshita Challa, Nolwazi Z Gcwensa, Dominic Hall, Douglas Nabert, Nicole Chambers, Ignacio Gallardo, Michael Millet, Laura Volpicelli-Daley, Mark S Moehle.

  Neuronal inclusions of α-synuclein (α-syn) are pathological hallmarks of Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). α-Syn pathology accumulates in cortical neurons which project to the striatum. To understand how α-syn pathology affects cortico-striatal synapses at early time points before significant dopamine neuron loss, pre-formed α-syn fibrils (PFF) were injected into the striatum to induce endogenous α-syn aggregation in corticostriatal-projecting neurons. Electrophysiological recordings of striatal spiny projection neurons (SPNs) from acute slices found a significant decrease in evoked corticostriatal glutamate release and corticostriatal synaptic release sites in mice with PFF-induced aggregates compared to monomer injected mice. Expansion microscopy, confocal microscopy and Imaris reconstructions were used to identify VGLUT1 positive presynaptic terminals juxtaposed to Homer1 positive postsynaptic densities, termed synaptic loci. Quantitation of synaptic loci density revealed an early loss of corticostriatal synapses. Immunoblots of the striatum showed reductions in expression of pre-synaptic proteins VGLUT1, VAMP2 and Snap25, in mice with α-syn aggregates compared to controls. Paradoxically, a small percentage of remaining VGLUT1+ synaptic loci positive for pS129-α-syn aggregates showed enlarged volumes compared to nearby synapses without α-syn aggregates. Our combined physiology and high-resolution imaging data point to an early loss of corticostriatal synapses in mice harboring α-synuclein inclusions, which may contribute to impaired basal ganglia circuitry in PD and DLB.

Keywords:  Dementia with Lewy bodies; Glutamatergic; Parkinson's disease; Striatum; Synapses; Α-Synuclein

DOI:  https://doi.org/10.1016/j.nbd.2025.106918
Int J Mol Sci. 2025 Mar 21. pii: 2867. [Epub ahead of print]26(7):

Lysosomal Dysfunction in Amyotrophic Lateral Sclerosis: A Familial Case Linked to the p.G376D TARDBP Mutation.

Roberta Romano, Victoria Stefania Del Fiore, Giorgia Ruotolo, Martina Mazzoni, Jessica Rosati, Francesca Luisa Conforti, Cecilia Bucci.

  Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Consequent to the loss of these cells, neuromuscular functions decline, causing progressive weakness, muscle wasting, and paralysis, leading to death in 2 to 5 years. More than 90% of ALS cases are sporadic, while the remaining 10% of cases are familial, due to mutations in 40 different genes. One of the most common genes to be mutated in ALS is TARDBP (transactive response DNA binding protein 43), which encodes TDP-43 (TAR DNA-binding protein 43). A mutation in exon 6 of TARDBP causes the aminoacidic substitution G376D in the C-terminal region of TDP-43, leading to its cytoplasmic mislocalization and aggregation. In fibroblasts derived from patients carrying this mutation, we found a strong increase in lysosome number, with overexpression and higher nuclear translocation of the transcription factor TFEB. In contrast, lysosomal functionality was deeply compromised. Interestingly, lysosomal activity was unaffected at an early stage of the disease, worsening in more advanced stages. Moreover, we observed the same pathological phenotype in iPSC (induced pluripotent stem cells)-derived patient motor neurons carrying the G376D mutation. Therefore, this mutation compromises the functionality of lysosomes, possibly contributing to neurodegeneration.

Keywords:  TDP-43; TFEB; amyotrophic lateral sclerosis; lysosome; neurodegeneration; neurodegenerative disease

DOI:  https://doi.org/10.3390/ijms26072867
ACS Chem Neurosci. 2025 Apr 14.

4-Amino-3',4'-dihydroxychalcone Increases Tau Dynamics in Phase-Separated Droplets and Inhibits Tau Aggregation.

Rajeshkumar S Gop, Rishav Adhikary, Anuradha Venkatramani, Neha Sengar, Inder Pal Singh, Dulal Panda.

  The aggregation of the microtubule-associated protein tau is a distinctive characteristic of several neurodegenerative disorders like Alzheimer's disease and frontotemporal dementia. Small-molecule inhibitors have been investigated as a potential therapy for tau aggregation-related diseases. Here, we identified 4-Amino-3',4'-dihydroxychalcone (4-ADHC), a substituted aminochalcone, as an inhibitor of different stages of tau aggregation, namely, liquid-liquid phase separation, oligomerization, and filamentation. Size exclusion chromatography, absorbance, and fluorescence spectroscopic experiments suggested that 4-ADHC bound to purified tau. The dissociation constant for the binding of 4-ADHC to tau was determined to be 5.1 ± 0.8 μM using surface plasmon resonance. The compound potently inhibited heparin and arachidonic acid-induced tau aggregation in vitro. However, 4-ADHC neither inhibited tubulin polymerization nor the enzymatic activity of alcohol dehydrogenase and alkaline phosphatase. Fluorescence recovery after photobleaching experiments showed that 4-ADHC increased tau dynamics in phase-separated droplets, suggesting that the compound impeded the maturation of the droplets by increasing their liquid-like behavior. Further, atomic force microscopy, dot blot assay, and dynamic light scattering experiments demonstrated that the compound suppressed tau oligomerization. In addition, 4-ADHC inhibited tau filamentation and disaggregated preformed filaments. Thus, 4-ADHC is a candidate for developing potent tau aggregation inhibitors.

Keywords:  4-aminochalcone; Alzheimer’s disease; FRAP; liquid−liquid phase separation; tau aggregation

DOI:  https://doi.org/10.1021/acschemneuro.4c00567
J Biochem. 2025 Apr 16. pii: mvaf017. [Epub ahead of print]

The potential of erythrocyte α-synuclein to differentiate dementia with Lewy bodies from Parkinson's and Alzheimer's diseases.

Ryosuke Amagai, Ryunosuke Hosoi, Sakura Yoshioka, Taiki Maruyama, Takayuki Kawai, Soroku Yagihashi, Hitoshi Nukada, Ryuji Sakakibara, Ayako Okado-Matsumoto.

  Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer's disease (AD). Early differentiation of these disorders is crucial for managing core symptoms; however, existing biomarkers remain insufficient. DLB shares motor and cognitive symptoms with Parkinson's disease (PD), and both are classified as synucleinopathies due to abnormal α-synuclein aggregation. Although α-synuclein is predominantly expressed in the central nervous system, it is also abundant in erythrocytes. Recent studies suggest a potential link between erythrocyte-derived α-synuclein and synucleinopathy pathology. Additionally, we previously reported that both erythrocytes and circulating medium and large extracellular vesicles (m/lEVs) in plasma from healthy subjects contain full-length and C-terminally truncated α-synuclein. In this study, we found that erythrocyte α-synuclein levels were significantly lower in DLB compared to AD, PD, and healthy controls. Furthermore, α-synuclein levels in circulating m/lEVs were elevated in patients with neurodegenerative diseases. These findings provide new insights into the role of peripheral α-synuclein and suggest its potential utility as a diagnostic marker for DLB. While further validation is needed, erythrocyte-derived α-synuclein may complement nuclear medicine assessments in distinguishing DLB from other neurodegenerative disorders.

Keywords:  Alzheimer's disease; Parkinson’s disease; dementia with Lewy bodies; erythrocytes; α-synuclein

DOI:  https://doi.org/10.1093/jb/mvaf017