1161 Expression Profile Analysis of Neurodegenerative Disease: Advances in Specificity and Resolution* Jason G. Glanzer, 1 Phillip G. Haydon, 2 and James H. Eberwine 1,3 (Accepted September 15, 2003) Microarray technology has become a common tool for developing expression profiles. Initially used in the analysis of cells lines and homogeneous tissues, this platform has been applied to more diverse tissues, such as the brain. Several neural disorders have already been profiled by microarrays using relatively large amounts of tissue. This data has unveiled many genes with dif- ferential expression between normal and diseased tissue that could potentially be used as gene markers for these afflictions. Because of the heterogeneity of the CNS, it is likely that small dif- ferences between gene expression in these studies would be enhanced by the sampling of a sub- set of cells based on these newly characterized gene markers. Subtraction of normal, unaffected cells from the sample may also result in a more accurate profile of a diseased cell. Expression profile studies from several neuropathological states are presented, with emphasis placed on those studies using small samples of cellular material and those using specialized methods of cell iso- lation and RNA amplification KEY WORDS: AIDS; Alzheimer; aRNA; dementia; expression profile; microarray; Parkinson; schizophrenia; single cell. INTRODUCTION Diseases of the central nervous system can be diffi- cult to assess and are often characterized by changes in motor function, or behavior, rather than morphological or histological alterations of the brain. The histological diag- nosis of Alzheimer’s disease (AD), for example, is given postmortem after identification of senile plaques in brain tissue (1). Parkinson’s disease (PD), a neurodegenerative disease diagnosed in patients presenting changes in move- ment and posture, is caused by degeneration of the sub- stancia nigra (2). The specific area and amount of tissue affected in the substancia nigra may cause different forms of PD to develop, possibly requiring different therapeu- tic interventions (3). However, histological assessment of PD patients is usually made postmortem as well (4). Other disorders, such as schizophrenia and AIDS-related dementia, have a less established pathology and do not have the advantage of involving tissues concentrated with affected cells that can be sampled for further study. Therefore, many diseases of the brain cannot be well characterized due to the inability of live tissue to be sam- pled and the problems associated with identifying what tissues or cell types in this complex organ are responsi- ble for the pathological conditions. Recent advances in molecular biology have led to a new approach in characterizing these diseases: expression profiling. Measurements of specific RNA content in brain 0364-3190/04/0600–1161/0 © 2004 Plenum Publishing Corporation Neurochemical Research, Vol. 29, No. 6, June 2004 (© 2004), pp. 1161–1168 * Special issue on Expression Profiling Within the Central Nervous System II. 1 Department of Pharmacology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania. 2 Department of Neuroscience, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania. 3 Address reprint requests to: James H. Eberwine, University of Pennsylvania, 3620 Hamilton Walk, 37 John Morgan Building, Philadelphia, Pennsylvania 19104. Tel: (215) 898-0420; Fax: (215) 573-2236; E-mail: eberwine@pharm.med.upenn.edu