Association of Younger Age and APOE ɛ4 Carrier Status with Cerebral Amyloid Angiopathy in Pure and Mixed Alzheimers Disease Neuropathology (P3-6.004)

Abstract

<h3>Objective:</h3> To determine how key clinical and neuropathology factors relate to the odds of cerebral amyloid angiopathy (CAA) at autopsy in both ‘pure Alzheimers Disease (AD)’ and mixed neuropathology of AD with Lewy body pathology (AD+LBP). <h3>Background:</h3> Presence of CAA has important therapeutic implications in the clinical decision to use new generation anti-amyloid therapies in AD. <h3>Design/Methods:</h3> A retrospective longitudinal cohort study was conducted among 2068 participants in the National Alzheimer Coordinating Center database with a mean interval of 5.7 (SD 2.8) years from initial visit to autopsy. These included autopsy-confirmed AD, n=1175 or AD +LBP, n=893 with CAA data. Correlations between CAA severity, Braak and neurotic scores and logistic regression models evaluating age (younger &lt;65yrs vs older≥65yrs), sex, APOE <i>ɛ4</i> carrier status, Braak stage and neuritic plaque score were completed in AD and mixed AD+LBP. <h3>Results:</h3> Younger age (O.R. 2.13, [95% CI, 1.33–3.33], p=0.002) and <i>APOE ɛ4</i> (O.R. 2.62, [95% CI, 1.94–3.56], p&lt;0.001) were significant predictors of CAA in AD, while <i>APOE ɛ4</i> (O.R. 3.18, [95% CI, 2.2–4.6], p&lt;0.001) was significant in AD+LBP. Only among older individuals in both groups, CAA severity correlated to Braak stage [AD ρ=0.12 (0.06, 0.18, p&lt;0.001), AD+LBP ρ=0.16 (0.09, 0.24, p&lt;0.001)] and neuritic score [AD ρ=0.10 (0.04, 0.16, p=0.002), AD+LBP ρ=0.12 (0.04, 0.19, p=0.002)]. When controlling for Braak stage, the odds of CAA were lower in AD among older age individuals [O.R. 0.50 (0.30–0.80), p=0.004] but not in AD+LBP [O.R. 0.92(0.56–1.53), p=0.75]. <h3>Conclusions:</h3> Younger age and <i>APOE ɛ4</i> carrier status had a higher odds of CAA despite controlling for Braak stage and neuritic plaque score in ‘pure AD’. Among older individuals higher Braak stage and neuritic plaque score were correlated to CAA severity in AD and AD+LBP. These results are of importance in the recognition of patients at the highest risk of CAA in both AD and mixed AD+LBP. <b>Disclosure:</b> Dr. Pillai has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Springer Nature. Dr. Pillai has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Current Treatment Options in Neurology. The institution of Dr. Pillai has received research support from Alzheimer’s Association. The institution of Dr. Pillai has received research support from Keep Memory Alive Foundation . The institution of Dr. Pillai has received research support from NIA. Dr. Pillai has received personal compensation in the range of $500-$4,999 for serving as a Reviewer with DOD. Dr. Pillai has received personal compensation in the range of $500-$4,999 for serving as a Reviewer with RGC Hong kong. James Bena has nothing to disclose. Dr. Leverenz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Leverenz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Leverenz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai.