Henry G. Stephenson (United States of America)
University of Wisconsin-Madison
Medicine
Henry is a PhD student in the Neuroscience Training Program at the University of Wisconsin-Madison. He received his bachelor’s degree in Biology from Birmingham-Southern College prior to working as a research assistant studying the neurobehavioral consequences of sleep restriction at the Naval Medical Research Unit-Dayton. In his current research, he explores the complex, multifaceted role of inflammation in the evolution of Alzheimer’s disease. In doing so, he hopes to understand both innate and environmental factors that moderate the speed, timing, and ultimate trajectory of neurodegeneration in AD to aid disease monitoring and the identification of potential targets for therapeutic intervention.

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HIGHER SOLUBLE TREM2 IN CEREBROSPINAL FLUID IS ASSOCIATED WITH SLOWER AGE-RELATED HIPPOCAMPAL ATROPHY AND COGNITIVE DECLINE IN PRECLINICAL ALZHEIMER’S DISEASE

Session Name
0390 - MICROGLIA, TREM2, NEUROINFLAMMATION (ID 87)
Session Type
SYMPOSIUM
Date
Wed, 16.03.2022
Session Time
04:15 PM - 06:00 PM
Room
ONSITE: 113
Lecture Time
04:30 PM - 04:45 PM
Presenter

Abstract

Aims

Higher soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF) has previously been linked with attenuated longitudinal brain atrophy and cognitive decline when assessed primarily among individuals with clinical MCI and AD. However, whether sTREM2 is associated with a protective effect preclinically is not known. Thus, the objective of this study was to assess whether higher baseline sTREM2 predicted slower age-related hippocampal atrophy and cognitive decline in preclinical AD.

Methods

Cognitively unimpaired participants with available lumbar puncture and longitudinal MRI and/or cognitive testing were considered preclinical and selected for analysis based on amyloid positivity as indexed by CSF amyloid-beta42/40 ratio. CSF sTREM2 was determined using a robust prototype assay as part of the Roche NeuroToolKit research platform. Linear mixed effects models with a random intercept tested whether higher baseline sTREM2 attenuated age-associated declines in ICV-adjusted hippocampal volume (N=80) as well as Rey Auditory Verbal Learning Test (RAVLT) total and long-delay recall scores (N=86), controlling for gender and years of education.

Results

figure.jpgSee Figure 1. Results indicated significant sTREM2 x age interactions, whereby individuals with higher baseline sTREM2 had slower age-related decline in mean hippocampal volume (p = .033) as well as total (p = .009) and long-delay RAVLT scores (p = .027).

Conclusions

These findings support prior studies suggesting that higher sTREM2 levels may attenuate clinical progression in AD and extend previous findings by examining the impact of sTREM2 among cognitively unimpaired individuals with AD pathologic change. sTREM2, even in preclinical stages, may be associated with resilience to the deleterious impacts of amyloid accumulation.

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