This proposal describes experiments to study expression of the Alzheimer's disease (AD) associated beta/A4 amyloid precursor protein (APP) in brain injury induced by ischemia. Brain tissue from rats subjected to focal or global cerebral ischemia will be analyzed immunochemically to evaluate the changes in distribution and time course of APP expression resulting from the insults. Further analyses by immunocytochemistry will entail identifying types of brain cells involved in altered APP expression after ischemic injury. For comparison, a small sample of brain tissues obtained at autopsy from humans who died with stroke episodes will be examined. Preliminary evidence from our laboratory suggests that APP immunoreactivity, detected by various antibodies to fragments of APP, is increased in perifocal regions and brain white matter of rats with permanent and reversible occlusions of the middle cerebral artery. These studies are based on the hypothesis that localized ischemic insults or cerebrovascular insufficiency leads to increased expression of APP in surviving brain cells. The project has direct relevance to AD in that chronic hypoperfusion or cerebrovascular insufficiency indicated by reduced cerebral blood flow may cause increased expression of APP which may in turn lead to deposition of the insoluble beta amyloid. It is expected that these studies will provide a basis for further intensive studies and open up therapeutic possibilities to impede the overexpression of APP or the aggregation of beta amyloid.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
2P50AG008012-06
Application #
3768243
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Moon, Heehyul; Townsend, Aloen L; Whitlatch, Carol J et al. (2017) Quality of Life for Dementia Caregiving Dyads: Effects of Incongruent Perceptions of Everyday Care and Values. Gerontologist 57:657-666
Moon, Heehyul; Townsend, Aloen L; Dilworth-Anderson, Peggye et al. (2016) Predictors of Discrepancy Between Care Recipients With Mild-to-Moderate Dementia and Their Caregivers on Perceptions of the Care Recipients' Quality of Life. Am J Alzheimers Dis Other Demen 31:508-15
Nagpal, Neha; Heid, Allison R; Zarit, Steven H et al. (2015) Religiosity and quality of life: a dyadic perspective of individuals with dementia and their caregivers. Aging Ment Health 19:500-6
Merritt, Marcellus M; McCallum, T J (2013) Too much of a good thing?: Positive religious coping predicts worse diurnal salivary cortisol patterns for overwhelmed African American female dementia family caregivers. Am J Geriatr Psychiatry 21:46-56
Reamy, Allison M; Kim, Kyungmin; Zarit, Steven H et al. (2013) Values and preferences of individuals with dementia: perceptions of family caregivers over time. Gerontologist 53:293-302
Pirisinu, Laura; Nonno, Romolo; Esposito, Elena et al. (2013) Small ruminant nor98 prions share biochemical features with human gerstmann-sträussler-scheinker disease and variably protease-sensitive prionopathy. PLoS One 8:e66405
Xiao, Xiangzhu; Yuan, Jue; Haïk, Stéphane et al. (2013) Glycoform-selective prion formation in sporadic and familial forms of prion disease. PLoS One 8:e58786
Zarit, Steven H; Lee, Jeong E; Barrineau, Mary J et al. (2013) Fidelity and acceptability of an adaptive intervention for caregivers: an exploratory study. Aging Ment Health 17:197-206
Binoy Mathew, K V; Eapen, Charu; Kumar, P Senthil (2012) Reliability and Concurrent Validity of Dynamic Rotator Stability Test-A Cross Sectional study. Indian J Physiother Occup Ther 6:76-81
Reamy, Allison M; Kim, Kyungmin; Zarit, Steven H et al. (2011) Understanding discrepancy in perceptions of values: individuals with mild to moderate dementia and their family caregivers. Gerontologist 51:473-83

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