# The role of astrogliosis in aging and the pathological and clinical progression of Alzheimer's Disease > **NIH NIH P01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $6,703,737 ## Abstract Overall Summary/Abstract Our research focuses on understanding the pathophysiological mechanisms that lead individuals to develop dementia, especially Alzheimer’s disease (AD). Our findings, as well as those from others, indicate that there is a complex interaction of clinical and subclinical cerebral and systemic factors during the pre-clinical phases of AD, some which convey vulnerability and some which convey resilience. The use of state-of-the-art technology is gradually providing us with better knowledge of the sequence of events and the role played by each risk factor. There is agreement among researchers that inflammation plays a critical role in the AD pathophysiological process, as noted in multiple pathological studies but examining inflammation in vivo has been challenging. To address these issues, we propose to characterize a new PET tracer, SMBT-1, that has high binding affinity for MAO-B, a proxy of astrogliosis. Astrogliosis is involved in Aβ deposition and alterations in cerebral blood flow and blood brain barrier integrity. One critical remaining question is the temporal relationship of astrogliosis to amyloid deposition, is astrogliosis reactive to Aβ deposition or does astrogliosis represent an additional “hit” exacerbating the effects of amyloid and tau pathology. The present PPG proposes to explore across 4 projects, the relationship of astrogliosis to AD pathology and risk factors using a combination of state-of-the-art neuroimaging, clinical, blood biomarker (and neuropathological tools. We propose to assemble a cohort of 300 participants age 55 and older who will complete annual neuropsychological, clinical, and blood examinations on all participants. At 24 and 48 months follow up evaluation will also include repeat PET and MRI scans to identify abnormalities and/or changes in Aβ and tau deposition, astrogliosis, brain structure and function to determine severity and progression of AD pathology, astrogliosis and cerebrovascular disease (CVD). Utilizing this cohort, Project 1 will focus on the hypothesis that astrogliosis augments, either directly or independently, the effects of Aβ and tau pathology as well as the effects of CVD on neurodegeneration (MRI) and cognition. In Project 2, we will explore the hypothesis that astrogliosis mediates the association between health risk factors (cardiovascular risk factors and sleep) and amyloid and tau pathology. Project-3 will utilize novel 7T MRI to assess the role of brain fluid dynamics in the pathway between astrogliosis and AD pathology. Finally, Project 4 will use the existing ADRC and PPG banked brains to characterize regional differences in SMBT-1 autoradiography and in vitro binding in relation to fine-grained immunohistochemical and biochemical analyses of MAO-B/GFAP astrogliosis, amyloid and tau pathology, vascular pathology, and synaptic markers in AD and non-AD autopsy brains, and it will ultimately characterize SMBT-1 PET in relation to neuropathology in postmortem br... ## Key facts - **NIH application ID:** 10851899 - **Project number:** 5P01AG025204-18 - **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH - **Principal Investigator:** HOWARD J AIZENSTEIN - **Activity code:** P01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $6,703,737 - **Award type:** 5 - **Project period:** 2004-12-01 → 2028-04-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10851899 ## Citation > US National Institutes of Health, RePORTER application 10851899, The role of astrogliosis in aging and the pathological and clinical progression of Alzheimer's Disease (5P01AG025204-18). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10851899. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*