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Ageing and Parkinson's disease: substantia nigra regional selectivity
Fearnley JM, Lees AJ.. Brain : a journal of neurology, 1991-10-01
Topic: Brain proteins, microglia and lab models
The micro-architecture of the substantia nigra was studied in control cases of varying age and patients with parkinsonism. A single 7 mu section stained with haematoxylin and eosin was examined at a specific level within the caudal nigra using strict criteria. The pars compacta was divided into a ventral and a dorsal tier, and each tier was further subdivided into 3 regions. In 36 control cases there was a linear fallout of pigmented neurons with advancing age in the pars compacta of the caudal substantia nigra at a rate of 4.7% per decade. Regionally, the lateral ventral tier was relatively spared (2.1% loss per decade) compared with the medial ventral tier (5.4%) and the dorsal tier (6.9%). In 20 Parkinson's disease (PD) cases of varying disease duration there was an exponential loss of pigmented neurons with a 45% loss in the first decade. Regionally, the pattern was opposite to ageing. Loss was greatest in the lateral ventral tier (average loss 91%) followed by the medial ventral tier (71%) and the dorsal tier (56%). The presymptomatic phase of PD from the onset of neuronal loss was estimated to be about 5 yrs. This phase is represented by incidental Lewy body cases: individuals who die without clinical signs of PD or dementia, but who are found to have Lewy bodies at post-mortem. In 7 cases cell loss was confined to the lateral ventral tier (average loss 52%) congruent with the lateral ventral selectivity of symptomatic PD. It was calculated that at the onset of symptoms there was a 68% cell loss in the lateral ventral tier and a 48% loss in the caudal nigra as a whole. The regional selectivity of PD is relatively specific. In 15 cases of striatonigral degeneration the distribution of cell loss was similar, but the loss in the dorsal tier was greater than PD by 21%. In 14 cases of Steele-Richardson-Olszewski syndrome (SRO) there was no predilection for the lateral ventral tier, but a tendency to involve the medial nigra and spare the lateral. These findings suggest that age-related attrition of pigmented nigral cells is not an important factor in the pathogenesis of PD.
Key findings
- Regionally, the lateral ventral tier was relatively spared (2.1% loss per decade) compared with the medial ventral tier (5.4%) and the dorsal tier (6.9%).
- These findings suggest that age-related attrition of pigmented nigral cells is not an important factor in the pathogenesis of PD.
Why it matters
In brain tissue from 36 people without Parkinson's disease, pigmented nerve cells in the substantia nigra declined by about 4.7% per decade, mostly in the dorsal tier; in 20 people with Parkinson's disease, the loss was heaviest in the lateral ventral tier (an average of 91%), which is the opposite pattern. The authors say this suggests that ordinary age-related cell loss is not an important driver of Parkinson's disease. The study is about Parkinson's disease, not Alzheimer's, and does not address treatment or prevention.
Study details
- Effect size4.7%; 2.1%; 5.4%
- Evidence strengthLow
How this study scored 56/100
Published in a leading specialty journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 1991 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 7 / 7 | Cited 3,529 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 95.4 citations a year over 37 year(s) since 1991 |
| Impact for its field and year | 4 / 6 | Cited 15.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 26 other studies in this library |
| Still being cited | 4 / 4 | Cited 396 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Andrew John Lees: h-index 166 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | National Hospital for Neurology and Neurosurgery: institution h-index 685 (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 1933245) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
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
Fearnley, J. M., & Lees, A. J. (1991). Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain : a journal of neurology. https://doi.org/10.1093/brain/114.5.2283
Vancouver
Fearnley JM, Lees AJ. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain : a journal of neurology. 1991. doi:10.1093/brain/114.5.2283. PMID: 1933245.
BibTeX
@article{fearnley1991-1933245,
author = {Fearnley, J. M. and Lees, A. J.},
title = {{Ageing and Parkinson's disease: substantia nigra regional selectivity}},
journal = {Brain : a journal of neurology},
year = {1991},
doi = {10.1093/brain/114.5.2283},
pmid = {1933245},
url = {https://doi.org/10.1093/brain/114.5.2283}
}
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