Affiliations: [a] Department of Chemistry, University of Kentucky, Lexington, KY, USA | [b] Department of Pathology, University of Kentucky, USA | [c] Sanders-Brown Center on Aging, Lexington, KY, USA | [d] Department of Internal Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA
Correspondence:
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Correspondence author: Tae H. Ji, Department of Chemistry, University of Kentucky, Lexington, KY 40515-0055, USA. Tel.: +1 859 257 3163; E-mail: tji@uky.edu.
Abstract: To identify genes aberrantly expressed in the brain of individuals with Alzheimer's Disease (AD), we analyzed RNA extracts from the hippocampus and cerebellum from 19 AD patients and 15 age- and sex-matched control subjects. Our analysis identified a number of genes that were over-expressed or under-expressed specifically in AD hippocampus. Among these genes, kalirin was the most consistently under-expressed in AD hippocampus, which was verified by semi-quantitative RT-PCR and real time PCR. Kalirin is predominantly expressed in the brain, particularly in the hippocampus, and plays crucial roles in neuronal stability and growth. Our observation is the first to relate kalirin to AD and a human disease. In addition to kalirin, the genes for voltage-gated Ca++ channel γ subunit 3 and visinin-like protein 1 (a Ca++ sensor protein) were under-expressed, whereas inositol 1,4,5-triphosphate 3-kinase B was over-expressed in AD hippocampus. Collectively, these differential expressions could severely impair calcium homeostasis. Remarkably, these aberrant gene expressions in AD hippocampus were not observed in AD cerebellum. Furthermore, housekeeping genes such as ribosomal protein genes are not affected by AD. These results provide new insights into the biochemistry of AD.
