Cholinergic dysfunction in diseases with Lewy bodies

Objective: To evaluate cholinergic activity in diseases with Lewy bodies (LB; LB variant of AD LBV, diffuse LB disease DLBD, and Parkinson’s disease PD) to determine if 1) AD changes are requisite to cholinergic dysfunction, 2) cholinergic activity declines to the same extent in neocortical and archicortical areas, and 3) cholinergic loss is influenced by APOE genotype. Background: Like AD, diseases with LB are associated with decreased choline acetyltransferase (ChAT) activity. Increased APOE ε4 allele frequency has been reported in LBV. Whether APOE genotype affects cholinergic function in LBV remains unclear. Methods: An autopsy series of 182 AD (National Institute on Aging and Consortium to Establish a Registry for Alzheimer’s Disease criteria), 49 LBV, 11 PD, 6 DLBD, and 16 normal control (NC) subjects. APOE genotype and ChAT activity (nmol/h/100 mg) in the midfrontal and hippocampal cortices were determined. Results: Mean midfrontal ChAT activity was markedly reduced in diseases with LB (LBV: 53.3 ± 39.0; PD: 54.8 ± 35.7; DLBD: 41.3 ± 24.8) compared to NC (255.4 ± 134.6; p p with (LBV) and without (DLBD and PD) AD pathology. Although mean ChAT activity for LBV was less than half that for AD in the midfrontal cortex, it was similar to that for AD in the hippocampus (LBV: 243.5 ± 189.7; AD: 322.8 ± 265.6; p > 0.05). However, hippocampal ChAT activity for both AD and LBV was lower than that for NC (666.5 ± 360.3; p Conclusions: Marked losses in midfrontal ChAT activity occur in diseases with LB, independent of coexistent AD changes. A greater midfrontal, as opposed to hippocampal, cholinergic deficit may differentiate LBV from AD. The lack of a relationship between ε4 allele dosage and midfrontal ChAT activity suggests that other factors may play a role in its decline in LBV.