Greater tau load and reduced cortical thickness in APOE ?4-negative Alzheimer's disease: a cohort study.

ABSTRACT: Alzheimer's disease is characterized by aggregated ?-amyloid and tau proteins, but the clinical presentations and patterns of brain atrophy vary substantially. A part of this heterogeneity may be linked to the risk allele APOE ?4. The spread of tau pathology is related to atrophy and cognitive decline, but little data exist on the effects of APOE ?4 on tau. The objective of this preliminary study was therefore to test if tau load and brain structure differ by APOE ?4 in Alzheimer's disease.Sixty-five ?-amyloid-positive patients at the prodromal and dementia stages of Alzheimer's disease were enrolled, including APOE ?4-positive (n?=?46) and APOE ?4-negative (n?=?19) patients. 18F-AV-1451 positron emission tomography was used to measure tau and brain magnetic resonance imaging (MRI) was used to measure cortical thickness.Compared with their APOE ?4-positive counterparts, APOE ?4-negative patients had greater tau load and reduced cortical thickness, with the most pronounced effects for both in the parietal cortex. Relative to the overall cortical tau load, APOE ?4-positive patients had greater tau load in the entorhinal cortex. APOE ?4-positive patients also had slightly greater cortical ?-amyloid load. There was an interaction between APOE ?4 and 18F-AV-1451 on cortical thickness, with greater effects of 18F-AV-1451 on cortical thickness in APOE ?4-negative patients. APOE ?4 and 18F-AV-1451 were independent predictors of cognition, but showed distinct associations with different cognitive tests.APOE genotype may be associated with differences in pathways in Alzheimer's disease, potentially through differential development and spread of tau, as well as through effects on cognitive outcomes involving non-tau-related mechanisms.

SUBMITTER: Mattsson N 

PROVIDER: S-EPMC6081879 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other