Effect of Aging and Dysfunction of Cerebral Microvasculature in Alzheimer’s Disease

Jorge Ghiso, PhD
NYU Langone Health (New York, NY)

Co-Principal Investigators

Agueda Rostagno, PhD
New York University School of Medicine (New York, NY)
Year Awarded:
2015
Grant Duration:
July 1, 2015 to June 30, 2019
Disease:
Alzheimer's Disease
Award Amount:
$250,000
Grant Reference ID:
A2015275S
Award Type:
Standard
Award Region:
US Northeastern

Recipient of The Virginia Faber Memorial Award for Alzheimer’s Disease Research.

Jorge Ghiso, PhD

Aging, Cerebral Amyloid Angiopathy, and Amyloid Beta Clearance

Summary

Alzheimer’s disease, the most common form of dementia, is characterized by fibrillar deposits of amyloid beta (Aβ) protein in brain tissue and cerebral blood vessels. The complex molecular mechanisms involved in the formation and accumulation of these deposits are not well understood; however, the brain’s failure to remove Aβ is increasingly recognized as a central element in the disease pathogenesis. Our preliminary data indicate that the action of brain enzymes and impaired clearance of the resulting degradation fragments via the blood and cerebrospinal fluid should not be overlooked as crucial contributors. The central focus of this project is how brain Aβ removal is additionally influenced by aging and by the dysfunction of the cerebral microvasculature. Using state of the art methodologies and genetically engineered mouse models with severely compromised cerebral blood vessels, this project will provide a better understanding how the brain degrades and removes Aβ in health and disease, an approach that will likely identify new targets for pharmacologic intervention.

Publications

Sotolongo K, Ghiso J, Rostagno A. Nrf2 activation through the PI3K/GSK-3 axis protects neuronal cells from Aβ-mediated oxidative and metabolic damage. Alzheimers Res Ther. 2020 Jan 13;12(1):13. doi: 10.1186/s13195-019-0578-9. PubMed PMID: 31931869; PubMed Central PMCID: PMC6958642 PubMed Icon Google Scholar Icon

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