Abstract
Background and Objectives: One of the most prevalent chronic diseases, osteoarthritis, may work in conjunction with apolipoprotein E-ε4 (APOE-ε4) to accelerate Alzheimer’s disease (AD) alterations, particularly in the primary motor (precentral) and somatosensory (postcentral) cortices. To understand the reasoning behind this, we investigated how osteoarthritis and APOE-ε4 influence the accumulation of β-amyloid (Aβ) and tau accumulation in primary motor and somatosensory regions in Aβ-positive (Aβ+) elderly adults.
Methods: We selected Aβ+ Alzheimer’s Disease Neuroimaging Initiative participants, defined by baseline 18F-florbetapir (FBP) Aβ PET standard uptake value ratio (SUVR) of AD summary cortical regions, who had longitudinal Aβ PET, the records of osteoarthritis medical history and APOE-ε4 genotyping. We examined how osteoarthritis and APOE-ε4 relate to baseline and longitudinal Aβ accumulation, 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 employing multiple comparisons correction.
Results: 374 individuals (mean age 75, 49.2% female, 62.8% APOE-ε4 carrier) 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 post-baseline FBP PET. Neither osteoarthritis nor APOE-ε4 was related to baseline FBP SUVR in precentral and postcentral regions. At follow-up, osteoarthritis rather than APOE-ε4 was associated with faster Aβ accumulation in postcentral (β=0.005[95% ci, 0.001, 0.008]) over time. In addition, osteoarthritis 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.
Glossary: Aβ: β-amyloid; AD: Alzheimer’s disease; CU: cognitively unimpaired; CI: cognitively impaired; MCI: mild cognitive impairment; OA: osteoarthritis; FBP: 18F-florbetapir; FTP: 18F-flortaucipir; PET: Positron emission tomography; SUVR: Standard uptake value ratio
- Received August 2, 2022.
- Accepted in final form March 17, 2023.
- © 2023 American Academy of Neurology
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