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 disease (AD) hippocampus demonstrated a 50% reduction in grain density for synaptophysin message over CA1 pyramidal neurons containing neurofibrillary tangles (NFT) relative to near neighbor NFT-free neurons. This decrease was not global, but was selective since message grain density for the lysosomal protein, cathepsin D, increased 33% in these neurons (relative to NFT-free neurons). Poly A+ message grain density decreased by 25% in NFT neurons. Percent of the cell body containing NFT correlated -0.35 (p < 0.0001) with grain density for synaptophysin message. These data verify the concept of altered profiles of gene expression as a function of disease state within single cells and suggest that events associated with NFT formation may lead to altered expression of synaptic messages.
Callahan
L M
LM
Department of Neurobiology & Anatomy, University of Rochester, New York 14642, USA.
Vaules
W A
WA
Coleman
P D
PD
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002402:Cathepsin D / Q000235:genetics*; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016014:Linear Models; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis*; D016708:Synaptophysin / Q000235:genetics*
D012333:RNA, Messenger; D016708:Synaptophysin; D002402:Cathepsin D