Association of APOE with tau-tangle pathology with and without ?-amyloid.

ABSTRACT: 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 ?-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 ?-amyloid and PHF-tau tangles in 8 brain regions. Linear regression was used to compare the relation of APOE ?4 and ?2 to PHF-tau-tangle density in persons with ?-amyloid relative to persons without ?-amyloid. We found an interaction between APOE ?4 carriers and presence of ?-amyloid (? = -0.968, p = 0.013) such that the association of APOE ?4 with PHF-tau tangles was much stronger in brains with ?-amyloid. Stratified analysis shows that the association of APOE ?4 with PHF-tau tangles was considerably stronger among those with ?-amyloid (? = 0.757, p = 1.1 × 10(-15)) compared to those without ?-amyloid which was not significant (? = -0.201, p = 0.424). Separately, APOE ?2 was associated with fewer tangles in brains with ?-amyloid (? = -0.425, p = 7.6 × 10(-4)) compared to those without ?-amyloid which was not significant (? = -0.102, p = 0.506). Thus, the presence of APOE ?4 and ?2 alleles was not associated with PHF-tau tangles in the absence of ?-amyloid. The data provide additional evidence that PHF-tau tangles in the absence of ?-amyloid may reflect a pathologic process distinct from Alzheimer's disease.

SUBMITTER: Farfel JM 

PROVIDER: S-EPMC4716785 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature