Comparison of the neurofibrillary pathology in Alzheimer's disease and familial presenile dementia with tangles.
Alzheimer's disease (AD) is characterised neuropathologically by the presence of abundant extracellular beta-amyloid deposits and intracellular neurofibrillary lesions consisting of neurofibrillary tangles, neuropil threads and senile plaque neurites which contain paired helical filaments (PHFs) made of hyperphosphorylated microtubule-associated protein tau. A new familial form of presenile dementia with neurofibrillary pathology and no beta-amyloid deposits has been described recently [Sumi et al. (1992) Neurology 42: 120-127]. We have compared the tau pathology in this familial form of presenile dementia with that of AD. To this end we have used electron microscopy, immunoblotting and immunohistochemistry with phosphorylation-dependent (PHF1, AT8, AT100, AT180, AT270, 12E8) and phosphorylation-independent (BR133, BR134) anti-tau antibodies. We show that in the two diseases dispersed PHFs are structurally, biochemically and immunologically identical; they are stained by all anti-tau antibodies used and on immunoblots PHF-tau appears as three major bands of 60, 64 and 68 kDa. However, while the anti-tau antibodies stain neurofibrillary tangles, neuropil threads and neuritic plaques in AD brain, no neuritic plaques are found in familial presenile dementia. These results indicate that in the two diseases tau undergoes the same modifications; they confirm that neurofibrillary tangles and neuropil threads like those in AD can exist independently of beta-amyloid deposits and that their presence is associated with dementia.
Spillantini
M G
MG
MRC Laboratory of Molecular Biology, Cambridge, UK.
Crowther
R A
RA
Goedert
M
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology*; D003704:Dementia / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D016874:Neurofibrillary Tangles / Q000473:pathology*; D016875:tau Proteins / Q000032:analysis
D016875:tau Proteins