4.3 Article

Pedunculopontine Cholinergic Cell Loss in Hallucinating Parkinson Disease Patients but Not in Dementia With Lewy Bodies Patients

Journal

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 72, Issue 12, Pages 1162-1170

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/NEN.0000000000000014

Keywords

Acetylcholine; Dementia with Lewy bodies; Parkinson disease; Parkinson disease with dementia; Pedunculopontine tegmental nucleus; Visual hallucinations

Funding

  1. Parkinson Patienten Vereniging
  2. Stichting Internationaal Parkinson Fonds (IPF), The Netherlands

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There is a cholinergic deficit in Parkinson disease (PD) and in dementia with Lewy bodies (DLB) that plays a role in a variety of clinical symptoms, including visual hallucinations (VH). The aim of this study was to assess cholinergic neuronal loss and PD and Alzheimer disease pathology in the pedunculopontine nucleus pars compacta (PPNc) of PD and DLB patients with VH. Postmortem brainstem tissue samples of 9 clinically diagnosed and pathologically confirmed PD patients with VH, 9 DLB patients with VH, and 9 age-and sex-matched nondemented controls were obtained from the Netherlands Brain Bank. Using a morphometric approach, we estimated the density of cholinergic neurons in the PPNc and determined the local load of alpha-synuclein-immunoreactive Lewy pathology, neurofibrillary tangles, and beta-amyloid plaques. Cholinergic cell density in the PPNc was significantly lower in PD compared with DLB patients with VH (-39%, p < 0.001) and controls (-41%, p < 0.001). Alpha-synuclein load was higher in PD, whereas beta-amyloid plaque pathology was more pronounced in DLB patients. The mean cell density in DLB patients was not significantly reduced compared with that in controls. These results may indicate different patterns of degeneration of cholinergic output structures in PD and DLB.

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