W. Sue T. Griffin, Ph.D. is a Professor and Vice Chairman of Research for the Department of Geriatrics. Her primary research focus is the cellular and molecular biology of aging, which encompasses mechanisms of gene action in the regulation of cellular aging, protein degradation, and mitochondrial dysfunction in normal and dystrophic muscle, in osteoporosis, and in Alzheimer’s disease (AD). Dr. Griffin’s research involves developmental biology of central nervous system-immune system interactions in health and disease and age related changes. She also serves as the Director of Research for the Geriatric Research Clinical Center at the Central Arkansas Veterans Healthcare System and is deeply involved with Alzheimer’s research. Dr. Griffin seeks the fundamental causes of AD and how this knowledge can be applied for treatment of patients and eradication of the disease.

Her work with postmortem brain tissue from AD patients demonstrated overexpression of IL-1 in activated microglia, overexpression of biologically active S100ß in activated astrocytes, and overgrowth of dystrophic neuronal processes (neurites) overexpressing ß-APP in ß-amyloid plaques. This past year Dr. Griffin’s group has shown that S100ß, like IL-1, regulates the expression of the proinflammatory protein IL-6.

Dr. Griffin’s work provides an explanation at the molecular level of why anti-inflammatory strategies may reduce the risk and or delay the onset of AD. In addition, it provides the molecular framework for future, more precise intervention strategies. In collaboration with Eli Lilly and Company (Indianapolis, Indiana), Dr. Griffin’s group has shown that in a transgenic mouse model of AD, S100ß is overexpressed months before the neuropathologic changes characteristic of AD appear.

Selected Publications:

Culpan D. MacGowan SH. Ford JM. Nicoll JA. Griffin WS. Dewar D. Cairns NJ. Hughes A. Kehoe PG. Wilcock GK. 2003 Tumour necrosis factor-alpha gene polymorphisms and Alzheimer’s disease. Neurosci Lett. 350:61-65.

Li Y, Liu L, Barger SW, Griffin WST. 2003 Interleukin-1 Mediates Pathological Effects of Microglia on Tau Phosphorylation and on Synaptophysin Synthesis in Cortical Neurons through a p38-MAPK Pathway. J Neurosci 23:1605-1611.

Li Y, Liu L, Barger SW, Griffin WST. 2004 Microglial activation by uptake of fragmented DNA via a scavenger receptor. J Neuroimmunol 147:5050-5055.

Wu S, Bodles AM, Porter MM, Griffin WST, Basile AS, Barger SW 2004 Potential Role for D-serine in Alzheimer’s disease. J Neuroinflammation 2004 Apr 20:1:2.

Griffin WST, Mrak RE. 2004 Cytokines and their potential as biomarkers: relevance to Down’s syndrome. J Policy Practices Cognitive Disorders (in press).

Mrak RE, Griffin WST 2004 Glia and Their Cytokines in Progression of Neurodegeneration. Neurobiol Aging (in press).

Mrak RE, Griffin WST 2004 Trisomy 21 and Brain. J Neuropathol Exp Neurol Ann Neurol 63:679-685.

Wainwright MS, Craft JM, Griffin WST, Marks A, Pineda J, Padgett K, Van Eldik LJ. 2004 Increased Susceptibility of S100B Transgenic Mice to Perinatal Hypoxia-Ischemia. Ann Neurol 56: 61-67.

Li Y, Liu L, Van Eldik LJ, Griffin WST, Barger SW. 2004 S100B-Induced Microglial and Neuronal IL-1 Expression is mediated by Cell Type-Specific transcription factors. J Neurochem (in press).