HAI Book 2025 - Flipbook - Page 438
Lao, Patrick
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TSPO PET mediates tau-associated neurodegeneration in limbic and
temporal regions across clinical variants of Alzheimer9s disease
Patrick Lao1, Aubrey Johnson1, Anna Smith1, Diana Guzman1, Hannah Houlihan1, Amarachukwu
Okafor1, Lauren Heuer1, Thairi Sanchez1, Daniel Talmasov1, Ndubisi Chikwem1, Dina Dass1,
James Noble1, William Kreisl1, Scott Small1
1
Columbia University Medical Center, New York, NY, US
Background: Microglia surveil the brain microenvironment and respond in neuroprotective and neurotoxic ways.
We investigated the role of microglia in individuals with ADRD, and hypothesized that microglia mediate
progressive associations between amyloid, tau, and neurodegeneration.
Methods: Participants (21 controls, 25 individuals with ADRD) from the Longitudinal Imaging of Microglial
Activation in Different Clinical Variants of Alzheimer9s Disease study underwent baseline amyloid PET
(Florbetaben SUVR), tau PET (MK6240 SUVR), TSPO PET (ER176 SUVR), and structural MRI (gray matter volume).
Consensus diagnosis (e.g., MCI, AD, PCA, FTD, LATE) was performed at the CUIMC ADRC. We assessed regional
TSPO mediations along key ATN pathways, adjusting for multiple comparisons. Sensitivity analyses were
performed stratified by amyloid positivity.
Results: TSPO mediated the association between tau and neurodegeneration in limbic and temporal regions (0.27 to -0.39, p
