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

Abstract

Background and objectives: One of the most prevalent chronic diseases, osteoarthritis (OA), may work in conjunction with APOE-ε4 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-ε4 influence the accumulation of β-amyloid (Aβ) and tau accumulation in primary motor and somatosensory regions in Aβ-positive (Aβ+) older individuals.

Methods: We selected Aβ+ Alzheimer Disease Neuroimaging Initiative participants, defined by baseline ¹⁸F-florbetapir (FBP) Aβ PET standardized uptake value ratio (SUVR) of AD summary cortical regions, who had longitudinal Aβ PET, the records of OA medical history, and APOE-ε4 genotyping. We examined how OA and APOE-ε4 relate to baseline and longitudinal Aβ accumulation and tau deposition measured at follow-up in precentral and postcentral cortical areas and how they modulate Aβ-associated future higher tau levels, adjusting for age, sex, and diagnosis and using multiple comparison corrections.

Results: A total of 374 individuals (mean age 75 years, 49.2% female, 62.8% APOE-ε4 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 ¹⁸F-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-ε4 was related to baseline FBP SUVR in precentral and postcentral regions. At follow-up, OA rather than APOE-ε4 was associated with faster Aβ accumulation in postcentral region (β = 0.005, 95% CI 0.001-0.008) over time. In addition, OA but not the APOE-ε4 allele was strongly linked to higher follow-up FTP tau levels in precentral (β = 0.098, 95% CI 0.034-0.162) and postcentral (β = 0.105, 95% CI 0.040-0.169) cortices. OA and APOE-ε4 were also interactively associated with higher follow-up FTP tau deposition in precentral (β = 0.128, 95% CI 0.030-0.226) and postcentral (β = 0.124, 95% CI 0.027-0.223) regions.

Discussion: This study suggests that OA was associated with faster Aβ accumulation and higher Aβ-dependent future tau deposition in primary motor and somatosensory regions, providing novel insights into how OA increases the risk of AD.