Preservation of nucleus basalis neurons containing choline acetyltransferase and the vesicular acetylcholine transporter in the elderly with mild cognitive impairment and early Alzheimer's disease

Immunocytochemistry for choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT) was used to examine the expression of the se linked cholinergic markers in human basal forebrain, including cases wit h early stages of Alzheimer's disease (AD). Previous neurochemical studies have measured decreased ChAT activity in terminal fields, but little change or even increased levels of VAChT. To determine total cholinergic neuron n umbers in the nucleus basalis of Meynert (nbM), stereologic methods were ap plied to tissue derived from three groups of individuals with varying level s of cognition: no cognitive impairment (NCI), mild cognitive impairment (M CI), and early-stage Alzheimer's disease (AD). Both markers were expressed robustly in nucleus basalis neurons and across all three groups. On average , there was no significant difference between the number of ChAT-(210,000) and VAChT- (174,000) immunopositive neurons in the nbM per hemisphere in NC I cases for which the biological variation was calculated to be 17%. There was approximately a 15% nonsignificant reduction in the number of cholinerg ic neurons in the nbM in the AD cases with no decline in MCI cases. The num ber of ChAT- and VAChT-immunopositive neurons was shown to correlate signif icantly with the severity of dementia determined by scores on the Mini-Ment al State Examination, but showed no relationship to apolipoprotein E allele status, age, gender, education, or postmortem interval when all clinical g roups were combined or evaluated separately. These data suggest that cholin ergic neurons, and the coexpression of ChAT and VAChT, are relatively prese rved in early stages of AD. (C) 1999 Wiley-Liss, Inc.