Abnormal Cholesterol Proces- Sing in Alzheimer’s Disease Patient’s Fibroblasts

s, provides the references for proceedings articles (published in Neurobiology of Lipids and elsewhere) and related bibliography. The entire collection of the neurobiology of lipids sessions at Neuroscience 2002 is also available (Neurobiology of Lipids, 2002, Vol. 1, 5, http://neurobiologyoflipids.org/content/1/5). © 2004 by the abstracts’ authors EDITOR’S PLATINUM CHOICE* Program number 420.11 ABNORMAL CHOLESTEROL PROCESSING IN ALZHEIMER’S DISEASE PATIENT’S FIBROBLASTS F. Dufour, W. Zhao, L. Ravindranath, D.L. Alkon Blanchette Rockefeller Neurosciences Institute, Rockville, MD, USA [email protected] Cholesterol has recently received attention as a potentially important factor in Alzheimer’s disease etiology. Caveolin, which binds cholesterol, plays a prominent role in cellular cholesterol transport. This protein is mainly located in plasma membrane invaginations called caveolae, which help determine cholesterol-dependent clustering of proteins involved in specific signal transduction pathways. Here, we report new clues about the involvement of caveolin in Alzheimer s disease. Cell fractions were collected for Western blotting with fibroblasts isolated from Alzheimer’s patients (AD) or age and sex matched controls (AC). While AC cells demonstrated higher levels of caveolin in membrane-enriched fractions compared with AD cells (p<0.05; n=6), more concentrated cholesterol and caveolin signals were found in the caveolaeenriched fractions from AD. Consistent immunocytochemistry results showed that caveolin was preferentially clustered on the plasma membrane in AD cells, whereas a more scattered signal was observed in AC cells. Furthermore, a cross-linking activation of the prion protein, which is known to link to signal transduction of caveolin, increased caveolin in AC membrane fractions (p<0.01; n=6), and induced the formation of clustered caveolin observed with immunocytochemistry. This stimulation had no effect on AD caveolin distribution. Our results suggest a dysregulation of cholesterol processing in AD fibroblasts. Preliminary results also suggest that caveolin-dependent signal transduction is also altered in AD. Similar dysregulation of cholesterol processing in the brain may contribute to the pathogenesis of AD.