Abstract

Parkinson's disease is defined clinically by motor dysfunction, but its pathology is not confined to nigral dopaminergic neurons. Prominent non-motor features including cognitive impairment, autonomic failure and sleep disturbance indicate widespread neurodegeneration that remains incompletely characterised. We pre-registered and conducted a multilevel meta-analysis of 166 case-control post-mortem studies published between 1963 and 2025, mapping neuronal loss across 85 brain regions, 38 cell types and 145 region-cell populations. The evidence base behind this map is thin. Only 4 of 145 populations are adequately powered, and 82% of Allen Brain Atlas regions have never been quantified in Parkinson's disease. A further 18 populations would reach adequate power with five or fewer additional studies, identifying an efficient route to closing current gaps. Noradrenergic neurons of the locus coeruleus degenerate to a similar extent as substantia nigra dopaminergic neurons, with both populations losing more than 60% of neurons. Cholinergic neurons of the basal nucleus and pedunculopontine tegmental nucleus and dopaminergic neurons of the ventral tegmental area show significant but less severe loss. These findings establish Parkinson's disease as a multi-system neurodegenerative disorder and expose key gaps and biases in the existing literature. ### Competing Interest Statement The authors have declared no competing interest. Nathan Skene is funded by the UK Dementia Research Institute and UKRI Future Leaders Fellowship JPTH is a National Institute for Health and Care Research (NIHR) Senior Investigator (NIHR203807). JPTH was supported by NIHR Bristol Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol and is a member of the MRC Integrative Epidemiology Unit at the University of Bristol. JPTH and SD were supported by the NIHR Applied Research Collaboration West (ARC West) at University Hospitals Bristol and Weston NHS Foundation Trust. The views expressed in this article are those of the authors and do not necessarily represent those of the NHS, the NIHR, MRC, or the Department of Health and Social Care. Samuel Burke is funded by the FRQS doctoral scholarship, Brain Canada and ASAP.