HAI Book 2025 - Flipbook - Page 460
Boon, Baayla
Neuropathologic and ARIA-related findings in aducanumab-treated
Alzheimer's disease: a postmortem analysis of superficial cortical Aβ
clearance
Baayla D.C. Boon1,2, Yoav Piura3, Jessica L. Chalk1, Christina M. Moloney1, Sarah J. Lincoln1,
Matthew H. Rutledge4, Derek R. Johnson5,7, Dennis W. Dickson1, Aivi T. Nguyen6, R. Ross
Reichard6, Jonathan Graff-Radford7, David S. Knopman7, Neill Graff-Radford3, Melissa E.
Murray1
1
Department of Neuroscience, Jacksonville, FL, US
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam University Medical Center, location Vrije
Universiteit Medical Center, Amsterdam, NL
3
Department of Neurology, Jacksonville, FL, US
4
Department of Quantitative Health Sciences, Jacksonville, FL, US
5
Department of Radiology, Rochester, MN, US
6
Department of Laboratory Medicine and Pathology, Rochester, MN, US
7
Department of Neurology, Rochester, MN, US
2
Background: Several monoclonal amyloid-´ (A´) antibodies, including aducanumab, have been tested to treat
Alzheimer9s disease (AD). Limited data is available on neuropathology after treatment or amyloid-related imaging
abnormalities (ARIA) side effects. We report on such data from five aducanumab-treated study participants with
AD.
Methods: Aducanumab-treated study participants who came to autopsy (n=5) were matched to AD controls (n=12)
based on the presence/type of autosomal dominant AD mutation, APOE genotype, age at cognitive symptom
onset, and sex. We assessed cognitive measures, 18F-florbetapir PET composite SUVr, ARIA risk factors, and AD
neuropathologic change. Brain regions affected along Thal amyloid phases were stained for A´ isoforms using
multiplex immunofluorescence. ARIA-affected brain regions were assessed using Perl9s Prussian blue, A´,
fibrinogen for blood brain barrier integrity, membrane attack complex (C5b-C9) for complement activation, and
activated microglia (IBA1, CD68).
Results: Study participants included four males and one female, each carrying at least one APOE ε4 allele. Two
carried a PSEN1 NM_000021.4:c.817G>A, p.Glu273Lys mutation. Two had ARIA on MRI. None cognitively benefitted
from the drug. In four study participants, the composite 18F-florbetapir SUVr declined by 0.3-0.4. Cumulative
dosage ranged between 53241 mg/kg and time between last infusion and death 5-41 months. In study participants,
A´ was cleared in cortical layer I (p
