Abstract

This is a renewal of additional studies of fundamental aspects of the neurobiology of Alzheimer's Disease. In Project I, will continue studies of the biochemistry and molecular biology of A68, the antigen recognized by the monoclonal antibody Alz-50. The antigen has been purified to homogeneity and sequencing studies are in progress. The purified antigen appears to contain a protein kinase activity. In Project II, will continue to investigate the nature of cDNA probes obtained using antibodies recognizing neurofibrillary tangles. A cDNA encoding a portion of the MAP2 sequence has been identified to contain the binding site for the regulatory subunit of the cyclic AMP dependent protein kinase. Possible abnormalities in the concentration of the regulatory subunit will be investigated. Interactions of proteins encoded by these and other cDNA's with other cellular proteins will be investigated. In Project III, Drs. Dickson, Mattiace and Yen will continue and extend their studies of senile plaque formation, extending studies of human brain by examination of microglial cells in tissue culture and studies of neuritic abnormalities in rat brain. A new project has been added, Dr. Hanna Ksiezak-Reding will investigate the involvement of posttranslational modifications of tau protein in tangle formation and neuritic abnormalities in Alzheimer's Disease. The possible role of alternate splice variants of tau will also be investigated in Alzheimer's Disease, and in brain development.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG006803-07
Application #
3091104
Study Section
Aging Review Committee (AGE)
Project Start
1987-08-01
Project End
1995-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Jicha, G A; Weaver, C; Lane, E et al. (1999) cAMP-dependent protein kinase phosphorylations on tau in Alzheimer's disease. J Neurosci 19:7486-94
Jicha, G A; O'Donnell, A; Weaver, C et al. (1999) Hierarchical phosphorylation of recombinant tau by the paired-helical filament-associated protein kinase is dependent on cyclic AMP-dependent protein kinase. J Neurochem 72:214-24
Dickson, D W (1999) Microglia in Alzheimer's disease and transgenic models. How close the fit? Am J Pathol 154:1627-31
Jicha, G A; Rockwood, J M; Berenfeld, B et al. (1999) Altered conformation of recombinant frontotemporal dementia-17 mutant tau proteins. Neurosci Lett 260:153-6
Kalcheva, N; Lachman, H M; Shafit-Zagardo, B (1999) Survey for CAG repeat polymorphisms in the human MAP-2 gene. Psychiatr Genet 9:43-6
Vincent, I; Zheng, J H; Dickson, D W et al. (1998) Mitotic phosphoepitopes precede paired helical filaments in Alzheimer's disease. Neurobiol Aging 19:287-96
Aronica, E; Dickson, D W; Kress, Y et al. (1998) Non-plaque dystrophic dendrites in Alzheimer hippocampus: a new pathological structure revealed by glutamate receptor immunocytochemistry. Neuroscience 82:979-91
Zhao, M L; Liu, J S; He, D et al. (1998) Inducible nitric oxide synthase expression is selectively induced in astrocytes isolated from adult human brain. Brain Res 813:402-5
Heitner, J; Dickson, D (1997) Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects. A retrospective postmortem immunocytochemical and histofluorescent study. Neurology 49:1306-11
Shafit-Zagardo, B; Kalcheva, N; Dickson, D et al. (1997) Distribution and subcellular localization of high-molecular-weight microtubule-associated protein-2 expressing exon 8 in brain and spinal cord. J Neurochem 68:862-73

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