Pedunculopontine cholinergic cell loss in hallucinating Parkinson disease patients but not in dementia with Lewy bodies patients.
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 α-synuclein-immunoreactive Lewy pathology, neurofibrillary tangles, and β-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 β-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.
From the Departments of Anatomy and Neurosciences, Section Quantitative Morphology (DHH, YG, PV, WDJvdB), Neurology (DHH, AMR, HWB, EMJF), and Pathology (AJMR), Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Dagmar Hyacintha
DH
Hepp
A M
AM
Ruiter
Y
Y
Galis
P
P
Voorn
A J M
AJ
Rozemuller
H W
HW
Berendse
E M J
EM
Foncke
W D J
WD
van de Berg
D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D059329:Cholinergic Neurons / Q000473:pathology*; D005260:Female; D006212:Hallucinations / Q000209:etiology* / Q000473:pathology*; D006801:Humans; D020961:Lewy Body Disease / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications*; D045042:Pedunculopontine Tegmental Nucleus / Q000473:pathology*; D011180:Postmortem Changes; D018709:Statistics, Nonparametric
D016229:Amyloid beta-Peptides; D002795:Choline O-Acetyltransferase