Biomedical Frontiers: Winter 1995, Vol.2, No.2
Untangling Alzheimer's Disease
Basic Studies on the Pathology of Alzheimer's Disease

B-amyloid peptides and plaques:

Dr. Frederick Maxfield, professor of pathology, studies the effect of B-amyloid peptide as well as amyloid plaques from AD brains on microglial cells. Among the effects studied are the generation of intracellular messengers and the release of cytokines, such as IL-1.

Role of IL-1 on neurofibrillary tangles:

Initial studies have shown that treatment of neonatal brain cells with IL-1 will lead to hyperphosphorylation of tau on sites abnormally phosphorylated in AD. Studies by Dr. Michael Shelanski, chair and Delafield Professor of Pathology, focus on the range of changes in tau induced by IL-1 and the physiological relevance of IL-1 induced alterations in tau in vivo and in vitro. The role of microglia and astrocytes in the IL-1 mediated alterations of tau is of particular interest.

Role of kinases phosphorylating tau:

Dr. Ronald Liem, professor of pathology, studies the role of cdk5, a highly expressed kinase active in the nervous system that phosphorylates tau and other proteins. Overexpression and inhibition of this kinase in transgenic mice are studied. Other protein kinases that phosphorylate tau will be looked for.

Role of phosphatases and tau:

Abnormal phosphorylation also can be controlled by phosphatases. Preliminary studies in the laboratory of Dr. Gregg Gundersen, assistant professor of anatomy and cell biology and pathology, have shown the presence of a microtubule-associated phosphatase. This phosphatase will be characterized and purified and the mechanism of its association with microtubules will be determined. The activity of the phosphatase toward phosphorylated targets such as tau and MAP2 will be measured, as will its activity in normal and AD brains.