DECREASED TRKA GENE-EXPRESSION WITHIN BASAL FOREBRAIN NEURONS IN ALZHEIMERS-DISEASE

IN situ hybridization for TrkA mRNA was combined with quantitative opt ical densitometry to evaluate whether the expression of this gene is a ltered within cholinergic basal forebrain neurons (CBF) in Alzheimer's disease (AD). TrkA mRNA within individual nucleus basalis neurons was significantly reduced (66%) in AD cases relative to aged controls. Re verse transcription polymerase chain reaction quantitative analyses co nfirmed that TrkA mRNA levels decreased markedly in AD. In contrast, e xpression of the gene coding for for the low affinity p75(NTR) was not significantly altered in AD relative to aged controls. These data ind icate that there is a selective defect in trkA gene expression in AD, supporting the hypothesis that the degeneration of CBF neurons seen in this disease results from impaired nerve growth factor trophic suppor t.