Thy1 Receptor in Alzheimer's Disease

     Thy- 1 is an abundant protein on the surface of nerve cells and has a role in the growth and regeneration of nerve cel ls. We have found that antibodies binding to Thy-1 promote the growth of neurites (axons and dendrites ) that extend from one nerve cell and normally contact others. Recently, we have also found that , in autopsy specimens from patients with Alzheimer’ s disease , the distribution of Thy-1 is strikingly abnormal in the hippocampus , a portion of the brai n severely affected by Alzhe imer’s . The Thy-1 abnormalities involve senile plaques and cells that conta in neurofibrillary tangles. (Plaques and tangles are the classic pathologic features of Alzhe i mer’s) . There are also more widespread abnormalities in the distribution of Thy-1 on neurites in keeping with recent observations that these structures are diffusely abnormal in Alzheimer’s . In preliminary experiments, we have also recently identified a natural Thy-1 receptor (a molecule to which Thy-1 binds). It is located on astrocytes, the cells that help support nerve cells . In preliminary work, we have found genetic material that codes for the receptor. In this grant, we propose to identify conclusively the receptor and genetic material coding for it, to study their distribution in normal brains and in Alzheimer’s, and to characterize their function by experiments on cells grown in culture. In view of the work we have already done , this may have important implications for understanding Alzheimer’s and perhaps even for treating Alzheimer’s and other disorders in which nerve cells and their neurites degenerate or suffer injury since the receptor or an analog for it might help to promote regeneration or to slow degeneration.