Parkinsonism in Alzheimer's disease without Lewy bodies in association with nigral neuron loss: A data-driven clinicopathologic study.

INTRODUCTION

Parkinsonism in patients with Alzheimer's disease (AD) is often attributed to Lewy-related pathology, given its high comorbidity. In the era of anti-amyloid therapy, recognizing parkinsonism caused by AD pathology is needed to optimize the treatment.

METHODS

This study aimed to quantitatively characterize parkinsonism and nigral neuropathology in AD without Lewy bodies (LB). Nigral neurons were counted automatically. Fine-tuned ChatGPT collected structured clinical data.

RESULTS

Among 635 AD patients without LB, 62 (9.7%) presented parkinsonism, which correlated with reduced nigral neuron density (p < 0.01). Tau burden did not explain the nigral neuronal loss. TAR DNA-binding protein 43 (TDP-43) pathology correlated with reduced nigral pigmented neuron density (p = 0.03).

DISCUSSION: Our findings suggest that parkinsonism in AD without LB is related to nigral neuronal loss in association with TDP-43 pathology. Recognition of parkinsonism in AD without LB is crucial for appropriate therapy.

HIGHLIGHTS: One in 10 Alzheimer's disease (AD) patients without Lewy bodies had parkinsonism. Parkinsonism in AD was correlated with reduced nigral neuron density. TAR DNA-binding protein 43 pathology was associated with nigral degeneration in AD. AD should be included in the differential diagnosis of dementia with parkinsonism.