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Neuropathology underlying clinical variability in patients with synucleinopathies
Halliday GM, Holton JL, Revesz T, Dickson DW.. Acta neuropathologica, 2011-07-01
Topic: Brain proteins, microglia and lab models
Abnormal aggregates of the synaptic protein, α-synuclein, are the dominant pathology in syndromes known as the synucleinopathies. The cellular aggregation of the protein occurs in three distinct types of inclusions in three main clinical syndromes. α-Synuclein deposits in neuronal Lewy bodies and Lewy neurites in idiopathic Parkinson's disease (PD) and dementia with Lewy bodies (DLB), as well as incidentally in a number of other conditions. In contrast, α-synuclein deposits largely in oligodendroglial cytoplasmic inclusions in multiple system atrophy (MSA). Lastly, α-synuclein also deposits in large axonal spheroids in a number of rarer neuroaxonal dystrophies. Disorders are usually defined by their most dominant pathology, but for the synucleinopathies, clinical heterogeneity within the main syndromes is well documented. MSA was originally viewed as three different clinical phenotypes due to different anatomical localization of the lesions. In PD, recent meta-analyses have identified four main clinical phenotypes, and clinicopathological correlations suggest that more severe and more rapid progression of pathology with chronological age, as well as the involvement of additional neuropathologies, differentiates these phenotypes. In DLB, recent large studies show that clinical diagnosis is too insensitive to identify the syndrome itself, although clinicopathological studies suggest variable clinical features occur in the different pathological forms of this syndrome (pure DLB, DLB with Alzheimer's disease (AD), and AD with amygdala predominant Lewy pathology). The recognition of considerable heterogeneity within the synucleinopathy syndromes is important for the identification of factors involved in changing their pathological phenotype.
Key findings
- In PD, recent meta-analyses have identified four main clinical phenotypes, and clinicopathological correlations suggest that more severe and more rapid progression of pathology with chronological age, as well as the involvement of additional neuropathologies, differentiates these phenotypes.
Why it matters
This review describes how abnormal α-synuclein deposits underlie synucleinopathies such as Parkinson's disease and dementia with Lewy bodies, and how additional pathologies may explain differences in clinical presentation. It is about understanding these diseases, not about treating, curing, or preventing Alzheimer's disease.
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Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 70/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Acta neuropathologica) |
| Journal's citation record | 3 / 4 | Acta Neuropathologica: journal h-index 287 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2011 — within 20 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 | A review of other studies — randomisation is not credited here |
| Times cited | 6 / 7 | Cited 431 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 25.4 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 4 / 6 | Cited 17.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 21 other studies in this library |
| Still being cited | 3 / 4 | Cited 66 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 | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21720849) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 70 / 100 | — |
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Read the original
May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Halliday, G. M., Holton, J. L., Revesz, T., & Dickson, D. W. (2011). Neuropathology underlying clinical variability in patients with synucleinopathies. Acta neuropathologica. https://doi.org/10.1007/s00401-011-0852-9
Vancouver
Halliday GM, Holton JL, Revesz T, Dickson DW. Neuropathology underlying clinical variability in patients with synucleinopathies. Acta neuropathologica. 2011. doi:10.1007/s00401-011-0852-9. PMID: 21720849.
BibTeX
@article{halliday2011-21720849,
author = {Halliday, G. M. and Holton, J. L. and Revesz, T. and Dickson, D. W.},
title = {{Neuropathology underlying clinical variability in patients with synucleinopathies}},
journal = {Acta neuropathologica},
year = {2011},
doi = {10.1007/s00401-011-0852-9},
pmid = {21720849},
url = {https://doi.org/10.1007/s00401-011-0852-9}
}
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