GENE-EXPRESSION IN ALZHEIMER NEOCORTEX AS A FUNCTION OF AGE AND PATHOLOGICAL SEVERITY

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