Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Parkinsonism in Alzheimer's disease without Lewy bodies in association with nigral neuron loss: A data-driven clinicopathologic study.
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Ono Daisuke, Sekiya Hiroaki, Maier Alexia R, Murray Melissa E, Koga Shunsuke, Dickson Dennis W
Аннотация
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.
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.