Objective: To determine whether loss of cholinergic projections to cortical and limbic regions contributes to the development of dementia in Parkinson’s disease (PD).

Background: PD is defined by the accumulation of aggregated alpha synuclein (Asyn) in Lewy bodies and Lewy neurites. As high as 80 percent of PD patients eventually develop dementia, which is associated with neocortical accumulation of Asyn and referred to as Lewy Body Dementia (LBD). However, neuronal loss and Asyn accumulation also occur in multiple subcortical nuclei, including cholinergic neurons in the nucleus basalis of Meynert, which have widespread projections to cortical and limbic regions.

Method: In this study, we analyzed a marker of cholinergic innervation in 8 different brain regions from PD autopsy cases with and without dementia. For comparison, we also analyzed the same 8 brain regions from control autopsy cases. We used sandwich ELISAs to analyze each brain region for choline acetyltransferase (ChAT), the enzyme responsible for acetylcholine synthesis.

Results: We observed significantly lower ChAT levels in PD compared to control cases for the five cortical regions that we analyzed. ChAT levels in cortical regions were lower in PD cases with dementia compared to those without dementia. Furthermore, the sum of ChAT levels in the five cortical regions inversely correlated with the Clinical Dementia Rating (CDR) sum of boxes score, a measure of global cognitive impairment.

Conclusion: These results indicate a role for the loss of cholinergic projections to cortical regions in the development of cognitive impairment in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cholinergic-deficits-in-parkinson-disease/