Lewy body pathology modifies risk factors for cerebral amyloid angiopathy when comorbid with Alzheimer's disease pathology

Abstract

Introduction: Cerebral amyloid angiopathy (CAA) often accompanies dementia-associated pathologies and is important in the context of anti-amyloid monoclonal therapies and risk of hemorrhage.

Methods: We conducted a retrospective neuropathology-confirmed study of 2384 participants in the National Alzheimer Coordinating Center cohort (Alzheimer's disease [AD], n = 1175; Lewy body pathology [LBP], n = 316; and mixed AD and LBP [AD-LBP], n = 893). We used logistic regression to evaluate age, sex, education, APOE ε4, neuritic plaques, and neurofibrillary tangles (NFTs) in CAA risk.

Results: APOE ε4 increased CAA risk in all three groups, while younger age and higher NFT stages increased risk in AD and AD-LBP. In AD-LBP, male sex and lower education were additional risk factors. The odds of APOE ε4 carrier homozygosity related to CAA was higher in LBP (25.69) and AD-LBP (9.50) than AD (3.17).

Discussion: AD and LBPs modify risk factors for CAA and should be considered in reviewing the risk of CAA.

Highlights: Lewy body pathology modifies risk factors for cerebral amyloid angiopathy (CAA) when present along with Alzheimer's disease (AD) neuropathology. In the context of anti-amyloid monoclonal therapies and their associated risks for hemorrhage, the risk of underlying CAA in mixed dementia with Lewy body pathology needs to be considered.

Keywords: APOE ε4; Alzheimer's; Lewy body; TDP‐43; cerebral amyloid angiopathy; mixed dementia; neuropathology.