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.
Showing the most recent 10 out of 39 publications
