A review of the literature suggests that several of the principal lesions of Alzheimer's lesion (AD) are present in a variety of conditions and represent a non-specific sustained molecular response to selected types of brain damage. We present evidence for amyloid toxicity in rat brain, plaque-associated and elevated basic FGF in the Alzheimer's brain and elevated basic FGF synthesis, and Alz-50, ubiquitin and beta protein immunoreactivity in response to injury in a rat model system. We propose to (1) quantify changes in basic FGF, Alz-50, ubiquitin, amyloid precursor protein (APP) and beta protein immunoreactivity induced in response to injury, (2) investigate the effect of immunoneutralization on microglial infiltration, reactive gliosis, AD antigens, and the synthesis of basic FGF, one of its receptor (Flg), and APP, (3) examine the effects of injury on the Alzheimer-related antigens, Alz-50, ubiquitin, beta protein, APP, and FGF by Western blot analysis, and (4) to determine the effects of injection of purified Alzheimer's brain plaque cores, (or control human brain extracts) and heparin beads (or beads alone) on infiltration of microglia, reactive gliosis, dendritic sprouting, AD antigens, dystrophic neurites, and sequestration of basic FGF and APP. Additional controls with synthetic amyloid and amyloid-related proteins will be used.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS030195-01
Application #
3417162
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1992-08-01
Project End
1996-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Whittier Institute for Diabetes & Endoc
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Cole, G M; Beech, W; Frautschy, S A et al. (1999) Lipoprotein effects on Abeta accumulation and degradation by microglia in vitro. J Neurosci Res 57:504-20
Frautschy, S A; Yang, F; Calderon, L et al. (1996) Rodent models of Alzheimer's disease: rat A beta infusion approaches to amyloid deposits. Neurobiol Aging 17:311-21