Association of APOE with tau-tangle pathology with and without β-amyloid.
This study tested the hypothesis that the association of apolipoprotein E (APOE) with paired helical filament tau (PHF-tau) tangle pathology differs in brains with and without β-amyloid. Participants were 1056 autopsied individuals from 2 clinical-pathologic cohort studies of aging and Alzheimer's disease (AD), the Religious Orders Study, and the Rush Memory and Aging Project. Neuropathologic measures were obtained using immunohistochemistry targeting β-amyloid and PHF-tau tangles in 8 brain regions. Linear regression was used to compare the relation of APOE ε4 and ε2 to PHF-tau-tangle density in persons with β-amyloid relative to persons without β-amyloid. We found an interaction between APOE ε4 carriers and presence of β-amyloid (β = -0.968, p = 0.013) such that the association of APOE ε4 with PHF-tau tangles was much stronger in brains with β-amyloid. Stratified analysis shows that the association of APOE ε4 with PHF-tau tangles was considerably stronger among those with β-amyloid (β = 0.757, p = 1.1 × 10(-15)) compared to those without β-amyloid which was not significant (β = -0.201, p = 0.424). Separately, APOE ε2 was associated with fewer tangles in brains with β-amyloid (β = -0.425, p = 7.6 × 10(-4)) compared to those without β-amyloid which was not significant (β = -0.102, p = 0.506). Thus, the presence of APOE ε4 and ε2 alleles was not associated with PHF-tau tangles in the absence of β-amyloid. The data provide additional evidence that PHF-tau tangles in the absence of β-amyloid may reflect a pathologic process distinct from Alzheimer's disease.
Department of Geriatrics, University of Sao Paulo Medical School, Sao Paulo, Brazil; Department of Pathology, Rush University Medical Center, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. Electronic address: farfel@usp.br.
Jose M
JM
Farfel
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Lei
L
Yu
Program in Translational NeuroPsychiatric Genomics, Departments of Neurology and Psychiatry, Institute for the Neurosciences, Brigham and Women's Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Philip L
PL
De Jager
Department of Pathology, Rush University Medical Center, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Julie A
JA
Schneider
Department of Geriatrics, University of Sao Paulo Medical School, Sao Paulo, Brazil; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
David A
DA
Bennett
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000483:Alleles; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D016875:tau Proteins
Apolipoprotein E; Neuropathology; Tau-tangle pathology; β-amyloid