ABSTRACT
During the prodromal and earliest stages of AD, there are alterations in the phenotypic expression of CBF neurons in subjects with mild cognitive impairment (MCI) and mild AD. Stereological counts revealed that during these early stages selective changes occur in markers that are co-localized within CBF neurons (Figure 32.1a). While the number of neurons expressing choline acetyltransferase (ChAT) or the vesicular acetylcholine transporter (VAChT) were unchanged in individuals with MCI and mild AD,9 the number of cholinergic neurons expressing p75 NTR 6 or trkA5 were significantly reduced (Figures 32.1a and 32.2). These observations support the emerging concept that there is an absence of frank degeneration of CBF neurons in MCI. Interestingly, the reduction of p75NTR 6 and trkA-positive5 neurons seen in MCI occurs in the presence of normal levels of
ChAT systems,5 suggesting that cholinergic enzyme loss is not an obligatory result of NGF receptor down-regulation at these early disease stages. Conversely, stable CBF neuronal numbers9 and cortical ChAT activity10,11 in MCI (Figures 32.1a and 32.3), suggest that compensa-
tory repair mechanisms support the viability of these cells.11 However, the possibility remains that the chronic reduction in both p75NTR and trkA is a factor underlying cholinergic dysfunction, and the subsequent extensive cholinergic deficit seen in end-stage AD.8
