Abstract

It is the goal of our Program Project to investigate the pathogenesis of neurofirbrillary tangles and neuritic and amyloid plaques in Alzheimer's disease. To do this we have developed an integrated program aimed at defining the constituent polypeptides of the amyloid fibers and paired helical filaments (PHF) by isolating and determining the amino acid sequence of the constituent polypeptides. This information will be used to prepare amyloid and PHF specific antibodies, cDNA probes, and synthetic amyloid and PHF peptides. These reagents will be used to (1) identify the cells responsible for abnormal fiber formation, (2) investigate the synthesis of amyloid and PHF polypeptides and their assembly in fibers, (3) identify amyloid and PHF specific epitopes and establish their structural relationship to amyloid fiber and PHF, and (4) identify and evaluate candidate precursor proteins in both the normal and AD/SDAT CNS, serum and CSF.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG004220-06
Application #
3090796
Study Section
Aging Review Committee (AGE)
Project Start
1987-07-01
Project End
1990-12-31
Budget Start
1989-07-01
Budget End
1990-12-31
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Institute for Basic Research in Dev Disabil
Department
Type
DUNS #
167205090
City
Staten Island
State
NY
Country
United States
Zip Code
10314

  Publications

Frackowiak, Janusz; Sukontasup, Thirasak; Potempska, Anna et al. (2004) Lysosomal deposition of Abeta in cultures of brain vascular smooth muscle cells is enhanced by iron. Brain Res 1002:67-75
Mazur-Kolecka, Bozena; Frackowiak, Janusz; Le Vine 3rd, Harry et al. (2003) TGFbeta1 enhances formation of cellular Abeta/apoE deposits in vascular myocytes. Neurobiol Aging 24:355-64
Frackowiak, Janusz; Miller, David L; Potempska, Anna et al. (2003) Secretion and accumulation of Abeta by brain vascular smooth muscle cells from AbetaPP-Swedish transgenic mice. J Neuropathol Exp Neurol 62:685-96
Mazur-Kolecka, Bozena; Frackowiak, Janusz; Kowal, Dagmar et al. (2002) Oxidative protein damage in cells engaged in beta-amyloidosis is related to apoE genotype. Neuroreport 13:465-8
Frackowiak, J; Mazur-Kolecka, B; Kaczmarski, W et al. (2001) Deposition of Alzheimer's vascular amyloid-beta is associated with decreased expression of brain L-3-hydroxyacyl-coenzyme A dehydrogenase (ERAB). Brain Res 907:44-53
Yang, S Y; He, X Y (2001) Role of type 10 17beta-hydroxysteroid dehydrogenase in the pathogenesis of Alzheimer's disease. Adv Exp Med Biol 487:101-10
Dolzhanskaya, N; Conti, J; Schwenk, V et al. (2001) Self-cleaving-ribozyme-mediated reduction of betaAPP in human rhabdomyosarcoma cells. Arch Biochem Biophys 387:223-32
Johnsingh, A A; Johnston, J M; Merz, G et al. (2000) Altered binding of mutated presenilin with cytoskeleton-interacting proteins. FEBS Lett 465:53-8
Bobinski, M; de Leon, M J; Wegiel, J et al. (2000) The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer's disease. Neuroscience 95:721-5
Wisniewski, H M; Wegiel, J; Vorbrodt, A W et al. (2000) Role of perivascular cells and myocytes in vascular amyloidosis. Ann N Y Acad Sci 903:18-Jun

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