Characterization of the Neuroinflammation in Autosomal Dominant Alzheimer Disease Using Neuro-Inflammation Imaging

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PROJECT SUMMARY/ABSTRACT Mounting evidence shows that immune system-mediated actions and neuroinflammation may contribute as much (or more) to Alzheimer disease (AD) pathogenesis as beta-amyloid and neurofibrillary tangle markers. Reliable, safe, and readily repeatable neuroinflammation tests during disease development have brought significant challenges in mechanistic research and therapy development. To address this unmet need, we developed neuro-inflammation imaging (NII), a quantitative imaging solution for neuroinflammation test. Based on diffusion magnetic resonance imaging (MRI), NII allows us to non-invasively, non-radioactively characterize the spatial distribution and temporal progression of neuroinflammation. The primary goal of this project is to cost-effectively characterize the role of neuroinflammation in AD using NII by retrospectively analyzing previously collected diffusion MRI data from the unique autosomal-dominant Alzheimer's disease (ADAD) cohort. Even though a relatively small proportion of cases of AD, ADAD present the similar pathological features to sporadic AD, has a predictable age at onset and low vascular risk factors due to the young age of the cohort, which makes the cohort very unique to determine the temporal evolution of neuroinflammation that culminates in AD. In this project, the trajectory of NII neuroinflammation biomarkers during the natural course of ADAD will be characterized and determined. The associations between whole- brain NII neuroinflammation biomarkers and CSF inflammation measures (sTREM2 and YKL40) will be examined. And the relationships among neuroinflammation measured by NII, amyloid deposition, and tauopathy measured by PET tracers will also be assessed. The successful retrospective analysis of previously collected diffusion MRI data in ADAD using NII will significantly enhance our understanding of the role of neuroinflammation in the initiation and progression of AD. The integration of NII neuroinflammation biomarkers into the DIAN and other clinical trial studies will provide neuroinflammation surrogate biomarkers complementary to other pathological measures for better AD diagnosis, prognosis, and treatment.