Neurotransmitter-mediated Neurovascular Coupling in Alzheimer’s Disease
Description: Alzheimer’s disease (AD) is the leading type of dementia that is affecting nearly 7 million Americans aged 65 and older. 2/3 of Americans with Alzheimer’s disease are women. While amyloid-ß and tau pathologies have long dominated AD research, recent findings highlight cerebral blood flow (CBF) dysregulation and neurovascular dysfunction as early contributors to AD pathogenesis. These vascular abnormalities contribute to blood-brain barrier (BBB) breakdown, neuroinflammation, and cognitive decline, also known as vascular contributions to impairment and dementia (VCID). Targeting novel pathways that affect AD progression is important due to limited treatment options. Dopamine and its receptors, particularly the D2 receptor (D2R), have been implicated in cerebrovascular regulation with decreased D2R in the hippocampus/cortex of AD patients. Although little is known about D2R signaling in the context of VCID, D2R is highly prevalent in the brain and is readily expressed on neurons and endothelial cells, which are key regulators of neurovascular coupling (NVC) and the blood-brain barrier (BBB) integrity. Therefore, we propose to investigate the role of D2R signaling to mitigate AD-induced neurovascular and behavioral dysfunction in 3xTg-AD mice. Our central hypothesis is quinpirole (selective D2R agonist) can prevent neurovascular uncoupling, BBB leakage, and improve functional outcomes in aged 3xTg-AD mice.
Funder: American Heart Association
Amount: $70,680
Funding type: training
Funder scheme: Predoctoral Fellowship
Start date: 2026-01-01
End date: 2027-12-31
Investigators: Julia Langman, Julia Langman
Institution: The University of Texas Health Science Center at Houston
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Funded outputs count: 0
Funder award ID: 26PRE1563496
OpenAlex ID: G7609333915