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Tau load is associated with apolipoprotein E genotype and the amount of amyloid β protein, Aβ 40 , in sporadic and familial Alzheimer's disease
Author(s) -
Thaker U.,
McDonagh A. M.,
Iwatsubo T.,
Lendon C. L.,
PickeringBrown S. M.,
A. Mann D. M.
Publication year - 2003
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1046/j.1365-2990.2003.00425.x
Subject(s) - apolipoprotein e , presenilin , allele , alzheimer's disease , genotype , missense mutation , degenerative disease , tau protein , pathology , biology , genetics , disease , medicine , mutation , gene
U. Thaker, A. M. McDonagh, T. Iwatsubo, C. L. Lendon, S. M. Pickering‐Brown and D. M. A. Mann (2003) Neuropathology and Applied Neurobiology 29, 35–44
Tau load is associated with apolipoprotein E genotype and the amount of amyloid β protein, Aβ 40 , in sporadic and familial Alzheimer's disease The total amount of hyperphosphorylated tau protein (p‐tau load), present as neurofibrillary tangles (NFTs), neuropil threads or plaque neurites, was quantified in the frontal cortex of 109 cases of sporadic Alzheimer's disease (AD) and 35 cases of familial AD due to missense mutations in the presenilin‐1, presenilin‐2 and amyloid precursor protein genes. p‐tau load was inversely correlated with age at onset of illness in both sporadic and familial AD but not with duration of disease. There was no difference in p‐tau load between cases of familial AD and others with sporadic AD, matching the familial cases for apolipoprotein E (APO E) genotype. However, p‐tau was greater in cases of familial and sporadic AD in the presence of APO E ɛ4 allele and increased with gene dose. Conversely, p‐tau load tended to be lower when ɛ2 allele was present. In sporadic AD, tau load was highly significantly correlated with amyloid β 40 (Aβ 40 ), but not Aβ 42(43) , load. These data indicate that the burden of pathological tau deposited in the brain in both familial and sporadic AD is favoured in the presence of APO E ɛ4 allele and also related to the amount of Aβ 40 , this also being higher when ɛ4 allele is present. Aβ 40 plaques are rich in microglial cells and it is possible that p‐tau pathology in AD is triggered by reaction of microglial cells to the presence of Aβ 40 and not this peptide directly.