Nigral cell loss pattern differs from ageing

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

J. M. Fearnley and Andrew J. Lees, National Hospital, Queen Square, London (PubMed affiliation). Funders are not stated in the abstract. Brain 114(5):2283–2301, 1991.

What happened

The substantia nigra is the brainstem region whose dopamine neurons die in Parkinson's (landmark 21). The authors counted pigmented neurons in one thin section at a fixed level of the caudal nigra. They split the pars compacta (the cell-dense band) into a ventral and a dorsal tier, each in three regions.

• Ageing, 36 controls: steady loss of 4.7% of pigmented cells per decade. The lateral ventral tier lost least (2.1% per decade); the medial ventral tier lost 5.4% and the dorsal tier 6.9%.
• Parkinson's, 20 cases: loss was exponential, about 45% in the first decade. The pattern was opposite to ageing: lateral ventral tier 91%, medial ventral 71%, dorsal 56%.
• Incidental Lewy body cases (people with Lewy bodies at autopsy but no symptoms; 7 cases): loss confined to the lateral ventral tier, average 52%.
• The authors estimated 68% loss in that tier, and 48% in the caudal nigra overall, at symptom onset, and a silent phase of about 5 years.
• In 15 cases of striatonigral degeneration (a related disorder), the pattern was similar but the dorsal tier lost 21% more than in Parkinson's.

Why it moved us toward a cure

It showed the vulnerability is specific, not just "old neurons die". That is the question the whole branch asks: what makes these cells fragile? Later work proposed answers such as calcium load (landmark 57) and a named cell subtype in the ventral nigra (landmark 99). The 68% figure, with the dopamine deficit of landmark 1, also gives a rough size for the loss any restorative therapy must replace.

Related work showed that calbindin-rich dopamine neurons are spared (landmark 343).

Outcome

Advanced. The spatial pattern has been widely cited since. It rests on one section per brain and small groups, and it describes where cells die, not why.

Sources

• Fearnley & Lees, Brain 1991;114:2283–2301, DOI 10.1093/brain/114.5.2283 (abstract via Europe PMC, PMID 1933245)
• Not yet verified: full text (only the abstract was read); how the 5-year silent phase was derived (the abstract says only "estimated"); whether later counts (stereology) confirm the percentages.