Alzheimer's disease (AD) involves the production of deposits of a protein which is normally produced, amyloid beta-protein (Ab). Genetic evidence suggests Ab may play a causal role. But with the probable exception of increased Ab, none of the factors promoting Ab deposition in vivo have been demonstrated. The investigators have developed experimental paradigms for exploring the Ab deposition process, and identified several variables (one with a possible role in FAD) which appear to promote blockable Ab deposits in tat brain; they propose to characterize these phenomena in detail, and to test other factors which may seed or promote deposits in the same model system. They propose to also investigate factors which may promote plaque progression after deposition and to further investigate our preliminary ultrastructural and immunohistochemical evidence for toxicity and to determine the relationship between toxicity and the degree of Ab aggregation. These experiments will provide the first example of a system where endogenous Ab deposits can be induced by injury or growth factors in a rat model, and where an important and manipulative risk factor for AD may be demonstrated along with a specific inhibitor.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG010685-05A1
Application #
2051945
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1991-09-29
Project End
2000-03-31
Budget Start
1995-04-10
Budget End
1996-03-31
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Attar, Aida; Ripoli, Cristian; Riccardi, Elisa et al. (2012) Protection of primary neurons and mouse brain from Alzheimer's pathology by molecular tweezers. Brain 135:3735-48
Frautschy, Sally A; Cole, Greg M (2011) What was lost in translation in the DHA trial is whom you should intend to treat. Alzheimers Res Ther 3:2
Frautschy, Sally A (2010) Thinking outside the box about COX-1 in Alzheimer's disease. Neurobiol Dis 38:492-4
Cole, Greg M; Frautschy, Sally A (2010) Mechanisms of action of non-steroidal anti-inflammatory drugs for the prevention of Alzheimer's disease. CNS Neurol Disord Drug Targets 9:140-8
Frautschy, Sally A; Cole, Greg M (2010) Why pleiotropic interventions are needed for Alzheimer's disease. Mol Neurobiol 41:392-409
Ma, Qiu-Lan; Galasko, Douglas R; Ringman, John M et al. (2009) Reduction of SorLA/LR11, a sorting protein limiting beta-amyloid production, in Alzheimer disease cerebrospinal fluid. Arch Neurol 66:448-57
Hu, Shuxin; Begum, Aynun N; Jones, Mychica R et al. (2009) GSK3 inhibitors show benefits in an Alzheimer's disease (AD) model of neurodegeneration but adverse effects in control animals. Neurobiol Dis 33:193-206
Hu, Shuxin; Ying, Zhe; Gomez-Pinilla, Fernando et al. (2009) Exercise can increase small heat shock proteins (sHSP) and pre- and post-synaptic proteins in the hippocampus. Brain Res 1249:191-201
Cole, Greg M; Teter, Bruce; Frautschy, Sally A (2007) Neuroprotective effects of curcumin. Adv Exp Med Biol 595:197-212
Ma, Qiu-Lan; Harris-White, Marni E; Ubeda, Oliver J et al. (2007) Evidence of Abeta- and transgene-dependent defects in ERK-CREB signaling in Alzheimer's models. J Neurochem 103:1594-607

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