A number of morphometric studies on dendritic extent in the aging mammalian central nervous system have demonstrated that aging neurons are capable of increasing the size and complexity of their dendritic trees. There is also evidence that an alliteration in this ability may play a role in the pathogenesis of Alzheimer's Disease (AD). Microtubule-associated proteins (MAPs) are a heterogeneous class of macromolecules which have been found to enhance the polymerization of tubulin into microtubules and to increase microtubule stability once polymerization has occurred. One of these MAPs, MAP 2 is a dendrite specific protein with two high molecular weight isoforms (2a and 2b) and one lower molecular weight isoform (2c). Since the amount of MAP 2 in a given brain region parallels the volume of the dendritic compartment in that same region, MAP 2 is a valuable marker for the quantification of dendritic extent. We propose to measure levels of MAP 2 mRNA in selected regions of AD and normal human brain as a function of age by hybridization to a MAP 2 specific synthetic oligonucleotide probe. Age-related increase in MAP2 in control brain would support the hypothesis of growth of dendrites with advancing age. Failure to find such an age-related increase in AD brain would be consistent with the hypothesis of a deficit in growth of dendrites in AD brain.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Unknown (R35)
Project #
5R35AG009016-03
Application #
3790397
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
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Yermakova, A; O'Banion, M K (2000) Cyclooxygenases in the central nervous system: implications for treatment of neurological disorders. Curr Pharm Des 6:1755-76
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Yermakova, A V; Rollins, J; Callahan, L M et al. (1999) Cyclooxygenase-1 in human Alzheimer and control brain: quantitative analysis of expression by microglia and CA3 hippocampal neurons. J Neuropathol Exp Neurol 58:1135-46
Morsch, R; Simon, W; Coleman, P D (1999) Neurons may live for decades with neurofibrillary tangles. J Neuropathol Exp Neurol 58:188-97
Callahan, L M; Vaules, W A; Coleman, P D (1999) Quantitative decrease in synaptophysin message expression and increase in cathepsin D message expression in Alzheimer disease neurons containing neurofibrillary tangles. J Neuropathol Exp Neurol 58:275-87
Yao, P J; Morsch, R; Callahan, L M et al. (1999) Changes in synaptic expression of clathrin assembly protein AP180 in Alzheimer's disease analysed by immunohistochemistry. Neuroscience 94:389-94

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