Small Research Grant Program for the Next Generation of Researchersin AD/ADRD Research

The objectives of this proposal are to optimize and validate detection and modeling of the multicomponent vascular and glymphatic systems in cerebral waste clearance (CWC) using superparamagnetic iron oxide (SPIO)-enhanced susceptibility weighted imaging (SWI, SPIO-SWI), and then to investigate CWC in the vascular and glymphatic systems during progression of Alzheimer’s Disease (AD). Emerging data indicate that the waste clearance from the brain parenchyma plays an important role in neurological diseases, especially neurodegenerative diseases. CWC is closely related to alterations in small blood and perivascular spaces of the brain. The glymphatic system and its peri-vascular pathway for waste clearance have been shown to be sensitive biomarkers for neurological diseases. Despite many milestone achievements, conclusive findings on the brain waste clearance relationships among the blood and perivascular spaces and their contributions to AD are absent. To date, CWC changes in the vascular and glymphatic systems and the outcomes during disease development as well as their relationships have not been investigated, which could provide mechanistic information about β- amyloid (Aβ) status during progression of AD. We have employed highly sensitive MRI methods using the SPIO- SWI to detect cerebral microvessels. Our preliminary data indicate that clearance of intracisternal injected MRI contrast agent decreases with AD severity and concomitantly with increased Aβ around the vasculature and functional deficits in a rat model of AD. Based on our novel preliminary data, we posit that the SPIO-SWI technique will significantly increase detection of microvessels in vascular and glymphatic systems and thereby permit detailed investigation of the interaction among the changes in cerebral blood vessels and perivascular spaces during progression of AD. To test these hypotheses, we will first (Aim 1) further optimize and validate our analytical and imaging approaches and then (Aim 2) investigate CWC under progression of AD. Data generated from this proposal will provide new insights into the relationships among the changes in small blood vessels, perivascular spaces, and the outcomes of diseases under AD condition. Moreover, all the MRI markers developed in this proposal can potentially be employed in the clinic for analysis of CWC in AD patients as well as patients with other neurodegenerative diseases. Project Number: 1R03AG098231-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Edward Boyd | Institution: HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES, EAST LANSING, MI | Award Amount: $314,000 | Activity Code: R03 | Study Section: Special Emphasis Panel[ZRG1 AN-W (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11284974