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Abstract Details

Cerebellar ARIA in a Patient With an APP Duplication Treated With Lecanemab
Aging, Dementia, and Behavioral Neurology
P12 - Poster Session 12 (11:45 AM-12:45 PM)
3-001
Case report of serious cerebellar ARIA in a participant with an APP gene duplication in the DIAN-TU-001 study receiving lecanemab.
Treatment with β-amyloid targeting antibodies (βATAs) carry a risk for amyloid related imaging abnormalities (ARIA) with either edema / effusion (ARIA-E) or hemorrhage (ARIA-H). Risks for ARIA include Apolipoprotein E ε4 and cerebral amyloid angiopathy (CAA).  ARIA-E is usually reported in the cerebral cortex, but rarely in the cerebellum.  βATAs have been studied in sporadic AD, but less so in Dominantly Inherited Alzheimer’s Disease.  
DIAN-TU-001 is a placebo-controlled, double-blind Phase II/III study evaluating the efficacy and safety of E2814 (antibody against the microtubule binding region of tau), administered alone or concurrently with lecanemab. Participants in DIAN-TU-001 all have mutations in the APP, PSEN1 or PSEN2 genes. This participant was in the symptomatic cohort (CDR=0.5–1) and was to receive open-label lecanemab followed by double-blind E2814. 

Participant genetics: APP gene duplication and ApoE ε3/ε3. Baseline MRI: 1 microhemorrhage each: right cerebellum and left insula. After the 4th infusion, a safety MRI showed widespread ARIA-E of the cerebellum and microhemorrhages in the cerebellum (7) and right occipital lobe (1). Cerebellar expansion caused a mild obstructive hydrocephalus, but a shunt was not needed. Treatment included high dose IV dexamethasone, and a tapering outpatient course of oral dexamethasone.

In the phase 3 study of lecanemab in early sporadic AD (CLARITY-AD) of 898 subjects treated with lecanemab, 3 (0.33%) had ARIA-E in the cerebellum, as an extension of occipital ARIA-E. There were no concurrent cerebellar signs and all resolved within 2 months.  

Cerebellar ARIA from βATAs is uncommon in sporadic AD.  This subject’s serious cerebellar ARIA-E/H may relate to an APP duplication, and possible evidence of CAA (microhemorrhage).  βATA use in patients with similar genotypes or Down’s syndrome should be approached carefully.
Authors/Disclosures
Darren R. Gitelman, MD, FAAN (Advocate Lutheran General Hospital)
PRESENTER 		The institution of an immediate family member of Dr. Gitelman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Astra Zeneca. The institution of Dr. Gitelman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. The institution of Dr. Gitelman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk. Dr. Gitelman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. The institution of Dr. Gitelman has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. An immediate family member of Dr. Gitelman has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for UpToDate. The institution of an immediate family member of Dr. Gitelman has received research support from Pfizer. The institution of an immediate family member of Dr. Gitelman has received research support from UCB. The institution of Dr. Gitelman has received research support from Biogen. The institution of Dr. Gitelman has received research support from Eisai. The institution of Dr. Gitelman has received research support from Lilly. The institution of Dr. Gitelman has received research support from Cassava. The institution of Dr. Gitelman has received research support from Wake Forest / Alzheimer's Association / NIH. The institution of Dr. Gitelman has received research support from Davos Alzheimer's Collaborative. The institution of Dr. Gitelman has received research support from Bristol Myers Squibb.
Jorge J. Llibre Guerra, MD (Knight Alzheimer's Disease Research Center) Dr. Llibre Guerra has nothing to disclose.
Eric M. McDade, DO (Washington University At St. Louis School of Medicine) Dr. McDade has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. McDade has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. McDade has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. McDade has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alzamend. Dr. McDade has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. McDade has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis. Dr. McDade has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche-Genentech. The institution of Dr. McDade has received research support from NIA. The institution of Dr. McDade has received research support from Eli Lilly. The institution of Dr. McDade has received research support from Hoffman-La Roche. The institution of Dr. McDade has received research support from Eisai. The institution of Dr. McDade has received research support from Eisai. Dr. McDade has received intellectual property interests from a discovery or technology relating to health care. Dr. McDade has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board Member with Fondation Alzheimer.
Lon Schneider, MD (USC School of Medicine) Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immue. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biovie. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Athira. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alpha-cognition. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Corium. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cortexyme. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurim Ltd. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Otsuka. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. The institution of Dr. Schneider has received research support from NIH. The institution of Dr. Schneider has received research support from Eli Lilly. The institution of Dr. Schneider has received research support from Biogen. The institution of Dr. Schneider has received research support from Biohaven.
Tammie Benzinger (Washington University) Tammie Benzinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Tammie Benzinger has received personal compensation in the range of $0-$499 for serving as a Consultant for Sora Neuroscience. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. Tammie Benzinger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Tammie Benzinger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson & Johnson. Tammie Benzinger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol, Myers Squibb. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for PeerView. Tammie Benzinger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medscape. The institution of Tammie Benzinger has received research support from Siemens. The institution of Tammie Benzinger has received research support from Hyperfine. Tammie Benzinger has a non-compensated relationship as a Consultant with Siemens that is relevant to AAN interests or activities. Tammie Benzinger has a non-compensated relationship as a Consultant with Eisai that is relevant to AAN interests or activities.
William C. Kreisl, MD Dr. Kreisl has received personal compensation for serving as an employee of Eisai Inc. Dr. Kreisl has received personal compensation for serving as an employee of Apellis Pharmaceuticals. An immediate family member of Dr. Kreisl has received personal compensation for serving as an employee of Novartis. Dr. Kreisl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Enigma.
Randall Bateman, MD (Washington Univ School of MedicinE) Dr. Bateman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for C2N Diagnostics . Dr. Bateman has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for C2N Diagnostics . Dr. Bateman has received stock or an ownership interest from C2N Diagnostics. The institution of Dr. Bateman has received research support from Alzheimer's SILQ Research Fund/ Barnes Jewish Hospital Foundation . The institution of Dr. Bateman has received research support from National Institutes of Health- R21AG067559. The institution of Dr. Bateman has received research support from Centene Corporation. The institution of Dr. Bateman has received research support from Rainwater Charitable Foundation . The institution of Dr. Bateman has received research support from Cure Alzheimer's Fund. The institution of Dr. Bateman has received research support from Cure Alzheimer's Fund. The institution of Dr. Bateman has received research support from Anonymous Foundation. The institution of Dr. Bateman has received research support from Cure Alzheimer's Fund. The institution of Dr. Bateman has received research support from BrightFocus Foundation. The institution of Dr. Bateman has received research support from Assn for Frontotemporal Degeneration FTD Biomarkers Initiative. The institution of Dr. Bateman has received research support from Rainwater Foundation. The institution of Dr. Bateman has received research support from NIH- R01NS095773. The institution of Dr. Bateman has received research support from AbbVie/Biogen/Eli Lilly. The institution of Dr. Bateman has received research support from NIH/NINDS/NIA- RF1AG061900 (R56AG061900 & R01NS065667). The institution of Dr. Bateman has received research support from Eisai. The institution of Dr. Bateman has received research support from Good Ventures Foundation. The institution of Dr. Bateman has received research support from National Institutes of Health- R01 AG070941. The institution of Dr. Bateman has received research support from National Institutes of Health-. The institution of Dr. Bateman has received research support from National Institutes of Health. The institution of Dr. Bateman has received research support from NIH- P50AG005681-36. The institution of Dr. Bateman has received research support from NIH/NIA- U19AG032438. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from Pharma Consortium. The institution of Dr. Bateman has received research support from Eli Lilly . The institution of Dr. Bateman has received research support from NIH/NIA- NIH R01AG053267. The institution of Dr. Bateman has received research support from Administrative Supplement 01- NIH . The institution of Dr. Bateman has received research support from Administrative Supplement 02- NIH . The institution of Dr. Bateman has received research support from NIH- 1U01AG059798. The institution of Dr. Bateman has received research support from NIH- R01AG068319. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from Roche. The institution of Dr. Bateman has received research support from NIH/NIA- R01AG046179. The institution of Dr. Bateman has received research support from GHR; Anonymous Foundation. The institution of Dr. Bateman has received research support from NIH/NIA- 1U01AG042791, 1U01AG042791. The institution of Dr. Bateman has received research support from Alzheimer's Association. The institution of Dr. Bateman has received research support from NIH/State Government- 5U19AG010483. Dr. Bateman has received intellectual property interests from a discovery or technology relating to health care.
David B. Clifford, MD, FAAN (Washington University School of Med) Dr. Clifford has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Excision BioTherapeutics. Dr. Clifford has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Seagen. Dr. Clifford has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CellEvolve. Dr. Clifford has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Wave Life Sciences. Dr. Clifford has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Clifford has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeuitics. Dr. Clifford has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Dr. Clifford has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Clifford has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity (Medpace). Dr. Clifford has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Clifford has received publishing royalties from a publication relating to health care.