Abstract Details

Title Microglia PET Imaging Pre- and Post- Anti-amyloid Treatment with Lecanemab: A Case Study

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P1 - Poster Session 1 (8:00 AM-9:00 AM)

Poster/Presentation
Number 12-008

Objective

To describe longitudinal human TSPO PET brain changes before and after treatment with lecanemab.

Background Lecanemab, a monoclonal antibody targeting soluble amyloid-β protofibrils, has shown efficacy in slowing cognitive decline in early Alzheimer’s disease. However, its impact on neuroinflammatory processes remains understudied. TSPO PET may offer insights into treatment-related changes in microglia.

Design/Methods A 71-year-old woman with amnestic mild cognitive impairment due to Alzheimer’s disease (CDR-global=0.5, CDR-SB=0.5, MMSE=29, FAQ=1) was enrolled in an observational imaging protocol (NCT04576793). TSPO PET (¹¹C-ER176) was performed 7 months prior to initiation of lecanemab and repeated after 19 biweekly 10mg/kg lecanemab infusions delivered over 9 months, during which time the patient had experienced no clinical or radiographic ARIA. Standardized uptake value ratios (SUVRs) were quantified relative to cerebellar gray matter defined by FreeSurfer 6.0. Cognitive testing and tau PET imaging (¹⁸F-MK6240) were also collected at each time point. TSPO and tau SUVR were standardized against annualized changes among amyloid-negative (non-AD) controls (n=10, age 54-80), adjusting for age, sex, BMI, APOE, and TSPO affinity. For this case study, the primary outcomes are regional changes in TPSO.

Results After 9 months of lecanemab treatment, the participant demonstrated mild improvement on memory measures (delayed episodic memory z-score change=107%) but without any change in MMSE or CDR-global. Greater increase in TSPO signal compared to controls was observed in occipital (pericalcarine=4.49SD), temporal (superior=4.49SD), parietal (superior=4.25SD), and frontal (caudal middle=4.14SD) lobes, as well as the hippocampus (3.65SD). Tau decreased in the frontal (caudal anterior cingulate=-2.08SD), temporal (entorhinal=-2.04SD) and parietal (isthmus=-1.69SD) lobes, as well as the parahippocampus (-2.62SD) and cerebellum (cortex=-2.45SD).

Conclusions This preliminary in vivo evidence suggests microglia recruitment and increased density may identify microglia-mediated clearance and brain maintenance functions. Systematic studies are warranted to confirm these findings and to clarify the relationship between treatment efficacy and microglial involvement.

Authors/Disclosures
Aubrey S. Johnson PRESENTER	Mrs. Johnson has nothing to disclose.
Zachary Smith, MD	Dr. Smith has nothing to disclose.
Michael -. Guzman	Mr. Guzman has nothing to disclose.
Hannah Houlihan	Miss Houlihan has nothing to disclose.
Kira E. Sanchez, Dr	Dr. Sanchez has nothing to disclose.
Scott A. Small, MD (Columbia Univserity Medical Center)	Dr. Small has received intellectual property interests from a discovery or technology relating to health care.
Stephanie Cosentino, PhD (Columbia University Medical Center)	Dr. Cosentino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Association for Frontotemporal Dementia. Dr. Cosentino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SAGE Pharmaceuticals.
James M. Noble, MD, FAAN (The Neurological Institute of New YorkTaubs Institute)	Dr. Noble has received stock or an ownership interest from NoMo Diagnostics. The institution of Dr. Noble has received research support from National Institute on Aging.
Patrick Lao, PhD	Prof. Lao has nothing to disclose.

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