Absence of abnormal hyperphosphorylation of tau in intracellular tangles in Alzheimer's disease.
Adult human nerve cells contain tau protein, a phosphorylated microtubule-associated protein, that is hyperphosphorylated in the fetus and in patients with Alzheimer's disease. Hyperphosphorylation, which diminishes the microtubule-binding capacity of tau, destabilizes microtubules and may enhance the formation of paired helical filaments that constitute neurofibrillary tangles in Alzheimer's disease. Here, we use phosphorylation-dependent anti-tau antibodies to detect specific epitopes that characterize hyperphosphorylated tau. Our demonstration of intracellular tangles containing full-length tau that are not immunolabeled by these antibodies suggests that hyperphosphorylation of tau is not obligatory in the formation of neurofibrillary tangles in Alzheimer's disease.
Bondareff
W
W
Department of Psychiatry and the Behavioral Sciences, University of Southern California Medical School, Los Angeles 90033, USA.
Harrington
C R
CR
Wischik
C M
CM
Hauser
D L
DL
Roth
M
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism*
D016875:tau Proteins; D016650:Fluorescein-5-isothiocyanate