Human serum stimulates Alzheimer markers in cultured hippocampal neurons.
The mechanism for promoting the distinct types of lesions in the Alzheimer disease (AD) brain and other changes outside the brain is unknown. We examined neurons in culture, unprotected by glia or a blood-brain barrier, to determine if exposure to serum from Alzheimer patients would affect markers for Alzheimer brain lesions. Rat hippocampal neurons were first grown for 4 days in a new serum-free culture medium, then exposed for 24 hr to human sera. Sera from 12 AD patients or their spouses increased four molecular markers characteristic of Alzheimer senile plaques and neurofibrillary tangles: Alz-50, beta-amyloid (beta/A4), MAP2, and ubiquitin, each with their expected cytologic distributions. Sera from ten young adults produced significantly less stimulation. By quantitative immunofluorescence, neuronal exposure to the elderly human sera produced 1.8- to 2.5-fold increases in mean fluorescent area/cell for each of these four markers relative to no serum exposure. As controls, an unrelated neuronal marker, enolase, was unaffected and fetal bovine serum did not stimulate immunoreactivity. Neuron viability and somal area were unaffected at 24 hours. The MAP2 increases were dose dependent with negligible effect at 2% serum and maximum effect at 10% serum after 24 hr. The MAP2 increase was greater after 48 hr of exposure than 24 hr and negligible at 2 hr. This stimulation of AD markers by human serum suggests that the genesis of both neuronal plaques and tangles may arise from access of toxic serum factors to susceptible neurons and/or failure to detoxify these factors.
Brewer
G J
GJ
Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield 62704-9230.
Ashford
J W
JW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014452:Ubiquitins / Q000276:immunology / Q000378:metabolism
C056167:Alzheimer's disease antigen; D016564:Amyloid beta-Protein Precursor; D000941:Antigens; D015415:Biomarkers; D008869:Microtubule-Associated Proteins; D014452:Ubiquitins; D010751:Phosphopyruvate Hydratase