Association of APOE-ε4, Osteoarthritis, Β-Amyloid, and Tau Accumulation in Primary Motor and Somatosensory Regions in Alzheimer Disease.

Background and ObjectivesOne of the most prevalent chronic diseases, osteoarthritis (OA), may work in conjunction with APOE-& epsilon;4 to accelerate Alzheimer disease (AD) alterations, particularly in the primary motor (precentral) and somatosensory (postcentral) cortices. To understand the reasoning behind this, we investigated how OA and APOE-& epsilon;4 influence the accumulation of & beta;-amyloid (A & beta;) and tau accumulation in primary motor and somatosensory regions in A & beta;-positive (A & beta;+) older individuals.MethodsWe selected A & beta;+ Alzheimer Disease Neuroimaging Initiative participants, defined by baseline F-18-florbetapir (FBP) A & beta; PET standardized uptake value ratio (SUVR) of AD summary cortical regions, who had longitudinal A & beta; PET, the records of OA medical history, and APOE-& epsilon;4 genotyping. We examined how OA and APOE-& epsilon;4 relate to baseline and longitudinal A & beta; accumulation and tau deposition measured at follow-up in precentral and postcentral cortical areas and how they modulate A & beta;-associated future higher tau levels, adjusting for age, sex, and diagnosis and using multiple comparison corrections.ResultsA total of 374 individuals (mean age 75 years, 49.2% female, 62.8% APOE-& epsilon;4 carriers) who underwent longitudinal FBP PET with a median follow-up of 3.3 years (interquartile range [IQR] 3.4, range 1.6-9.4) were analyzed, and 96 people had F-18-flortaucipir (FTP) tau PET measured at a median of 5.4 (IQR 1.9, range 4.0-9.3) years postbaseline FBP PET. Neither OA nor APOE-& epsilon;4 was related to baseline FBP SUVR in precentral and postcentral regions. At follow-up, OA rather than APOE-& epsilon;4 was associated with faster A & beta; accumulation in postcentral region (& beta; = 0.005, 95% CI 0.001-0.008) over time. In addition, OA but not the APOE-& epsilon;4 allele was strongly linked to higher follow-up FTP tau levels in precentral (& beta; = 0.098, 95% CI 0.034-0.162) and postcentral (& beta; = 0.105, 95% CI 0.040-0.169) cortices. OA and APOE-& epsilon;4 were also interactively associated with higher follow-up FTP tau deposition in precentral (& beta; = 0.128, 95% CI 0.030-0.226) and postcentral (& beta; = 0.124, 95% CI 0.027-0.223) regions.DiscussionThis study suggests that OA was associated with faster A & beta; accumulation and higher A & beta;-dependent future tau deposition in primary motor and somatosensory regions, providing novel insights into how OA increases the risk of AD.