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Alpha-synuclein pathology does not predict extrapyramidal symptoms or dementia
Parkkinen L, Kauppinen T, Pirttilä T, Autere JM, Alafuzoff I.. Annals of neurology, 2005-01-01
Topic: Brain proteins, microglia and lab models
Intracytoplasmic aggregation of alpha-synuclein protein as Lewy bodies in the brainstem neurons is diagnostic for Parkinson's disease, whereas if this process also occurs in the cortical neurons, it is considered pathognomonic for dementia with Lewy bodies. However, the link between alpha-synuclein incorporation into inclusions, neuronal dysfunction, and clinical symptoms needs to be clarified. Another important issue of the pathogenetic puzzle is to understand where alpha-synuclein pathology begins and how it progresses in the brain. To study this, we collected all cases from autopsy material (N = 904) that had alpha-synuclein pathology in the dorsal motor nucleus of vagus, substantia nigra, and/or basal forebrain nuclei. In this way, our study has a unique design because the selection of material is entirely based on the presence of alpha-synuclein pathology regardless of clinical phenotype. Retrospective clinical assessment then showed that only 32 (30%) of 106 alpha-synuclein-positive cases were diagnosed with a neurodegenerative disorder. The distribution or load of alpha-synuclein pathology did not permit a dependable postmortem diagnosis of extrapyramidal symptoms or cognitive impairment. Some neurologically unimpaired cases had a reasonable burden of alpha-synuclein pathology in both brainstem and cortical areas, suggesting that alpha-synuclein-positive structures are not definite markers of neuronal dysfunction.
Key findings
- Retrospective clinical assessment then showed that only 32 (30%) of 106 alpha-synuclein-positive cases were diagnosed with a neurodegenerative disorder.
- Some neurologically unimpaired cases had a reasonable burden of alpha-synuclein pathology in both brainstem and cortical areas, suggesting that alpha-synuclein-positive structures are not definite markers of neuronal dysfunction.
Why it matters
Researchers selected autopsy cases purely because their brains contained alpha-synuclein deposits (the protein that forms Lewy bodies), regardless of symptoms in life. Looking back at clinical records, only 32 of 106 such cases (30%) had been diagnosed with a neurodegenerative disorder. The amount or location of the deposits did not dependably indicate whether a person had movement symptoms or cognitive impairment. Because some people with no neurological impairment had "a reasonable burden" of these deposits, the study concludes they are "not definite markers of neuronal dysfunction".
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Study details
- Participants904
- Evidence strengthLow
How this study scored 52/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (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 | 1 / 5 | 2005 — older than 20 years, still counted |
| Sample size | 2 / 4 | 904 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 316 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.7 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 4 / 6 | Cited 11.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 18 other studies in this library |
| Still being cited | 2 / 4 | Cited 29 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Irina I. Alafuzoff: h-index 80 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Kuopio University Hospital: institution h-index 529 (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 15562510) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
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Read the original
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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
Parkkinen, L., Kauppinen, T., Pirttilä, T., Autere, J. M., & Alafuzoff, I. (2005). Alpha-synuclein pathology does not predict extrapyramidal symptoms or dementia. Annals of neurology. https://doi.org/10.1002/ana.20321
Vancouver
Parkkinen L, Kauppinen T, Pirttilä T, Autere JM, Alafuzoff I. Alpha-synuclein pathology does not predict extrapyramidal symptoms or dementia. Annals of neurology. 2005. doi:10.1002/ana.20321. PMID: 15562510.
BibTeX
@article{parkkinen2005-15562510,
author = {Parkkinen, L. and Kauppinen, T. and Pirttilä, T. and Autere, J. M. and Alafuzoff, I.},
title = {{Alpha-synuclein pathology does not predict extrapyramidal symptoms or dementia}},
journal = {Annals of neurology},
year = {2005},
doi = {10.1002/ana.20321},
pmid = {15562510},
url = {https://doi.org/10.1002/ana.20321}
}
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