Previous studies have shown a marked decline in neuronal and an increase in glial gene expression in Alzheimer's disease (AD) neocortex. Severity of pathologic changes may be greater in presenile AD (PAD) than in senile AD (SAD). We evaluated whether changes in transcript expression were altered as a function of age or pathologic severity. Northern analysis revealed a marked (> 50%) decline in expression of transcripts for the neurofilament light subunit and the major amyloid precursor protein (APP) isoforms in both PAD and SAD. Expression of these neuronal transcripts declined as a function of age in AD and control cases. Expression of the glial fibrillary acidic protein (GFAP) transcript was increased in AD, particularly in the presenile group. AD cases with larger numbers of neurofibrillary tangles had higher levels of GFAP transcript; AD cases with larger numbers of senile plaques had higher levels of APP695 transcript. We conclude that the neuronal mRNA decrements of AD are superimposed on an age-related decline. Age-related shift in expression of certain genes may account for the differences in pathologic severity of PAD and SAD.