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Neuropathology and molecular diagnosis of Synucleinopathies
Koga S, Sekiya H, Kondru N, Ross OA, Dickson DW.. Molecular neurodegeneration, 2021-12-18
Topic: Brain proteins, microglia and lab models
Synucleinopathies are clinically and pathologically heterogeneous disorders characterized by pathologic aggregates of α-synuclein in neurons and glia, in the form of Lewy bodies, Lewy neurites, neuronal cytoplasmic inclusions, and glial cytoplasmic inclusions. Synucleinopathies can be divided into two major disease entities: Lewy body disease and multiple system atrophy (MSA). Common clinical presentations of Lewy body disease are Parkinson's disease (PD), PD with dementia, and dementia with Lewy bodies (DLB), while MSA has two major clinical subtypes, MSA with predominant cerebellar ataxia and MSA with predominant parkinsonism. There are currently no disease-modifying therapies for the synucleinopathies, but information obtained from molecular genetics and models that explore mechanisms of α-synuclein conversion to pathologic oligomers and insoluble fibrils offer hope for eventual therapies. It remains unclear how α-synuclein can be associated with distinct cellular pathologies (e.g., Lewy bodies and glial cytoplasmic inclusions) and what factors determine neuroanatomical and cell type vulnerability. Accumulating evidence from in vitro and in vivo experiments suggests that α-synuclein species derived from Lewy body disease and MSA are distinct "strains" having different seeding properties. Recent advancements in in vitro seeding assays, such as real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), not only demonstrate distinct seeding activity in the synucleinopathies, but also offer exciting opportunities for molecular diagnosis using readily accessible peripheral tissue samples. Cryogenic electron microscopy (cryo-EM) structural studies of α-synuclein derived from recombinant or brain-derived filaments provide new insight into mechanisms of seeding in synucleinopathies. In this review, we describe clinical, genetic and neuropathologic features of synucleinopathies, including a discussion of the evolution of classification and staging of Lewy body disease. We also provide a brief discussion on proposed mechanisms of Lewy body formation, as well as evidence supporting the existence of distinct α-synuclein strains in Lewy body disease and MSA.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Koga, S., Sekiya, H., Kondru, N., Ross, O. A., & Dickson, D. W. (2021). Neuropathology and molecular diagnosis of Synucleinopathies. Molecular neurodegeneration. https://doi.org/10.1186/s13024-021-00501-z
Vancouver
Koga S, Sekiya H, Kondru N, Ross OA, Dickson DW. Neuropathology and molecular diagnosis of Synucleinopathies. Molecular neurodegeneration. 2021. doi:10.1186/s13024-021-00501-z. PMID: 34922583.
BibTeX
@article{koga2021-34922583,
author = {Koga, S. and Sekiya, H. and Kondru, N. and Ross, O. A. and Dickson, D. W.},
title = {{Neuropathology and molecular diagnosis of Synucleinopathies}},
journal = {Molecular neurodegeneration},
year = {2021},
doi = {10.1186/s13024-021-00501-z},
pmid = {34922583},
url = {https://doi.org/10.1186/s13024-021-00501-z}
}
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Key findings
- It remains unclear how α-synuclein can be associated with distinct cellular pathologies (e.g., Lewy bodies and glial cytoplasmic inclusions) and what factors determine neuroanatomical and cell type vulnerability.
- Accumulating evidence from in vitro and in vivo experiments suggests that α-synuclein species derived from Lewy body disease and MSA are distinct "strains" having different seeding properties.
Why it matters
This review sorts the α-synuclein diseases into two groups: Lewy body disease (Parkinson's disease, Parkinson's disease with dementia and dementia with Lewy bodies) and multiple system atrophy. It describes how lab seeding tests such as RT-QuIC and PMCA "offer exciting opportunities for molecular diagnosis using readily accessible peripheral tissue samples," but it reports no accuracy figures. It also says "there are currently no disease-modifying therapies for the synucleinopathies," and it does not address Alzheimer's disease directly.
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Study details
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular neurodegeneration) |
| Journal's citation record | 2 / 4 | Molecular Neurodegeneration: journal h-index 164 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 341 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 48.7 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 18.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 4 / 4 | Cited 250 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Dennis W. Dickson: h-index 218 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Mayo Clinic in Florida: institution h-index 681 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34922583) |
| Free to read | 2 / 2 | Free to read |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13024-021-00501-z
- PubMed: 34922583
- Original source →
- Free full text: Molecular Neurodegeneration →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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