Penn Alzheimer's Disease Core Center Pilot Research Grants
The NIH-funded Penn Alzheimer's Disease Core Center was able to award 2 full Pilot Research Grants in support of disease research. Congratulations to this year's awardees.
- John A. Detre, MD
"Novel MRI Biomarkers for Cerebrovascular Pathology in Dementia"
Abstract:
Although Alzheimer’s disease and cerebrovascular disease have traditionally been considered as distinct etiologies for dementia, a growing body of evidence suggests that there are strong reciprocal interactions between these disease processes, and that up to half of dementia patients have mixed syndromes with elements of both Alzheimer’s disease and cerebrovascular disease. Cases of cerebrovascular disease presenting with overt stroke or blockages in large arteries are readily recognizable, but identification of underlying cerebrovascular disease in the absence of these conditions is more difficult, and risk factors for cerebrovascular disease and Alzheimer’s disease overlap. The presence of ischemic-appearing lesions on brain MRI scans is currently the best screening method for underlying cerebrovascular disease, but such lesions are nonspecific and can occur in other disorders and pathologies. This project will evaluate three novel biomarkers of cerebrovascular disease that might be used to stratify patients with dementia or milder cognitive complaints. One approach will examine microvascular perfusion based on magnetically labeled arterial blood water. A second approach will utilize ultra-high-resolution MRI at 7 Tesla to look for subtle ischemic lesions not observable at standard clinical field strengths. The third approach will used dynamic MRI angiography to measure the compliance of the cerebrovascular circulation as a measure of pathological changes in arteries. This project will also bring together investigators with multidisciplinary expertise. - Edward B. Lee, MD, PhD
"Genomic Targets of Leptin Receptor Signaling in Alzheimer’s Disease"
Abstract:
Midlife obesity is a risk factor for Alzheimer’s disease (AD), but the molecular mechanisms linking these two disorders are unknown. Leptin signaling is known to be altered in response to both obesity and aging, and leptin modulates amyloid plaque pathology in transgenic mice through largely unknown mechanisms. Leptin’s main physiologic role is to regulate peripheral metabolism by acting on leptin receptor (LR)-expressing neurons within the CNS which triggers intracellular signaling pathways. Leptin-Jak2-STAT3 signaling is particularly important in the regulation of energy balance, but surprisingly little is known about the downstream targets of leptin-STAT3 signaling, and even less is known about how leptin-STAT3 signaling affects AD pathways. I propose studying LR signaling in vivo by (1) discovering the genomic targets of leptin-STAT3 in normal and obese mice and (2) understanding how STAT3 signaling affects APP processing and amyloid beta production.
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