Microglia PET Imaging Pre- and Post- Anti-amyloid Treatment with Lecanemab: A Case Study
Aubrey Johnson1, Anna Smith2, Diana Guzman2, Hannah Houlihan2, Thairi Sanchez2, Scott Small2, Stephanie Cosentino2, James Noble2, Patrick Lao2
1School of Medicine, New York Medical College, 2Department of Neurology, Columbia University Irving Medical Center
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.
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