Quantitative decrease in synaptophysin message expression and increase in cathepsin D message expression in Alzheimer disease neurons containing neurofibrillary tangles

Combining immunocytochemistry with in situ hybridization of Alzheimer disea se (AD) hippocampus demonstrated a 50% reduction in grain density for synap tophysin message over CA1 pyramidal neurons containing neurofibrillary tang les (NFT) relative to near neighbor NFT-free neurons. This decrease was not global, but was selective since message grain density for the lysosomal pr otein, cathepsin D, increased 33% in these neurons (relative to NFT-free ne urons). Poly A+ message grain density decreased by 25% in NFT neurons. Perc ent of the cell body containing NFT correlated -0.35 (p < 0.0001) with grai n density for synaptophysin message. These data verify the concept of alter ed profiles of gene expression as a function of disease state within single cells and suggest that events associated with NFT formation may lead to al tered expression of synaptic messages.