Thalamic cholinergic innervation is spared in Alzheimer disease compared to parkinsonian disorders

Abstract

There are two major sources of cholinergic projections in the brain. The nucleus basalis of Meynert provides the principal cholinergic input of the cortical mantle and the pedunculopontine nucleus–laterodorsal tegmental complex (PPN–LDTC; hereafter referred to as PPN) provides the major cholinergic input to the thalamus. Cortical cholinergic denervation has previously been shown to be part of Alzheimer and parkinsonian dementia but there is less information about subcortical thalamic cholinergic denervation. We investigated thalamic cholinergic afferent integrity by measuring PPN–Thalamic (PPN–Thal) acetylcholinesterase (AChE) activity via PET imaging in Alzheimer (AD), Parkinson disease without dementia (PD), Parkinson disease with dementia (PDD) and dementia with Lewy bodies (DLB). AD (n=13; mean age 75.4±5.5), PD (n=11; age 71.4±6.4), PDD (n=6; age 70.8±4.7), DLB (n=6; age 68.0±8.6) and normal controls (NC; n=14; age 69.0±7.5) subjects underwent AChE [11C]-methyl-4-piperidinyl propionate (PMP) PET imaging. PPN–Thal PET data were analyzed using the Nagatsuka method. There were no significant differences in mean age between the groups (F=1.86, p=0.134). Kruskal–Wallis testing demonstrated a significant group effect for PPN–Thal AChE hydrolysis rates (F=9.62, p<0.0001). Compared to NC, reduced thalamic k3 hydrolysis rate was noted in subjects with PDD (−19.8%; AChE k3 hydrolysis rates 0.1072±0.0143min−1), DLB (−17.4%; 0.1103±0.0112min−1) and PD (−12.8%; 0.1165±0.0114min−1). Each of these 3 subgroups was statistically different from AD subjects (−0.7%; 0.1326±0.0095min−1) who showed relatively spared thalamic k3 hydrolysis rates which were comparable to NC (0.1336±0.0142min−1). Thalamic cholinergic denervation is present in PD, PDD, and DLB but not in AD. Neurodegenerative involvement of thalamic cholinergic afferent projections may contribute to disease-specific motor and cognitive abnormalities.