The Role of Chemical Messenger Signaling in Removing Alzheimer's Pathology From the Brain

The contribution of cerebral amyloid (Abeta) angiopathy (CAA) and cerebrovascular pathology to the progression of Alzheimer’s disease (AD) has received renewed interest in the field. This proposal expounds upon compelling preliminary data to test that degeneration of the locus coeruleus (LC) and cholinergic basal forebrain (CBF) projection systems contributes to cognitive impairment through their damaging effects on intramural peri-arterial drainage (IPAD) of Abeta contributing to AD/CAA.

The contribution of cerebral amyloid (Aβ) angiopathy (CAA) to the progression of Alzheimer’s disease (AD) has received renewed interest in the field. This proposal expounds upon compelling preliminary data to test that degeneration of the locus coeruleus (LC) and cholinergic basal forebrain (CBF) projection systems contributes to cognitive impairment through their damaging effects on the vascular clearance of Aβ, thus contributing to AD/CAA. If successful, this proposal will advance the clinical rationale for targeting LC/CBF-mediated cerebrovascular dysfunction as a disease modifying strategy.