Biochemical analysis of tau proteins in argyrophilic grain disease, Alzheimer's disease, and Pick's disease : a comparative study.
Although argyrophilic grain disease is characterized histopathologically by tau-positive lesions known as argyrophilic grains located predominantly in limbic brain regions in the absence of other diagnostic neuropathologies, the biochemical correlates of argyrophilic grains in gray and white matter have not been reported. Thus, we analyzed insoluble (pathological) tau proteins in five argyrophilic grain disease brains in comparison with those seen in Alzheimer's disease and Pick's disease. Analyses of separately dissected gray and white matter samples from various cortical regions revealed that pathological tau in argyrophilic grain disease was confined primarily to mediotemporal neocortical gray and adjacent white matter, and also to the allocortex, amygdala, and hippocampus. The amounts of sarcosyl-insoluble tau in all five cases were substantially lower than in Alzheimer's disease and Pick's disease, but the amounts of sarcosyl-insoluble tau in white matter were higher or comparable to that detected in gray matter from the same region, which distinguishes argyrophilic grain disease from Alzheimer's disease. The banding patterns of tau isoforms in argyrophilic grain disease varied: in three cases they were similar to Alzheimer's disease, but in two other cases, 4 microtubule binding repeat (4R) tau predominated, which distinguishes argyrophilic grain disease from classical Pick's disease. The differences between these three diseases were re-enforced by the predominance of straight tau filaments from argyrophilic grain disease brains. Thus, we conclude that argyrophilic grain disease is a distinct tauopathy characterized by prominent accumulation of argyrophilic grains in limbic brain regions in association with the characteristic tau biochemical and ultrastructural profile reported here.
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001927:Brain Diseases / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020774:Pick Disease of the Brain / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism*
D016875:tau Proteins