An Investigation of the APOE4 Association with Tau Pathology and Cognitive Decline

Purpose The aim of this study was to evaluate the association between amyloid and tau pathology and cognitive decline with APOE4 carriership. Methods Individuals with varying degrees of cognitive impairment from a memory clinic (N=132) and a population-based (N=112) cohort underwent amyloid and tau positron emission tomography (PET) and APOE genotyping, and clinical and neuropsychological assessments were selected. Amyloid uptake was converted into centiloid values, and tau was quantified as standardised uptake value ratio (SUVR), normalised to the cerebellar crus. Subjects were classified as APOE4 carriers (if they had at least one E4 allele) and non-carriers. Linear regression models were used to assess the effect of APOE4 carriership on tau deposition by amyloid status. A sub-sample of 197 individuals underwent a follow-up neuropsychological assessment at least 1 year after baseline. A linear mixed model was used to assess whether APOE4 carriership predicted longitudinal changes in MMSE scores. Results Mean (SD) age of participants was 71.8 (7.9) years, 57% were men, 32% were APOE4 carriers, 38% were amyloid-positive (A+), and 47% were cognitively unimpaired. Carriers, as compared to non-carriers, showed significantly higher centiloid and tau SUVR values in all regions ( p <0.01). APOE4 carriers presented a faster cognitive decline compared to non-carriers ( =-0.82, p <0.01) even after correcting for amyloid and tau burden. Conclusion APOE4 carriers present an increase in both tau and amyloid deposition and faster cognitive decline compared to non-carriers. Results were affected by amyloid status, but not by the amount of accumulated amyloid. Carriership was a predictor of cognitive decline, even after accounting for amyloid and tau deposition, suggesting a possible independent effect of APOE4.