2008 Awardees

Investigator: Ci-Di Chen, PhD
Project Title: The role of the anti-aging protein Klotho in Alzheimer’s disease animal models

Klotho functions as an aging-suppressor, which, in mice, extends life span when overexpressed and accelerates the development of aging-like phenotypes when disrupted. Thus, a reduction in Klotho levels is detrimental to the entire organism. Findings in a mouse model of Alzheimer’s disease (AD) demonstrate that aged mice with amyloid plaques have markedly decreased Klotho expression in the brain compared to same age littermates without plaques. We are investigating a possible connection between AD and Klotho. It is known that age-associated oxidative damage may contribute to AD pathogenesis. We hypothesize that Klotho, as an anti-aging hormone and a regulator of anti-oxidative stress, will have beneficial effects on the onset of Abeta-induced neuronal deficits and that reducing Klotho would accelerate pathogenesis. We will test our hypothesis by crossing Klotho over-expressing mice or Klotho-deficient mice with AD mouse models and evaluate the development of the AD-like pathogenesis in these mice. We expect that Klotho overexpression will have beneficial effects on the onset of Abeta-induced deficits. Conversely, we expect that Klotho knock-down will accelerate AD-like progression. This study is expected to provide critical information for a better understanding of the aging process and Alzheimer’s disease, and also to provide targets for pharmacologic interventions.

Investigator: Brandon E. Gavett, PhD
Project Title: Ecological Validity of Neuropsychological Assessment in Dementia

The goal of this project is to establish the ecological validity of a formal office-based assessment, including the Daily Living tests from the Neuropsychological Assessment Battery (NAB), by empirically determining how accurately the information gathered during the office assessment corresponds to an in vivo evaluation of a participant’s functioning at home. To achieve this goal, the study will use a criterion-related validity approach that includes several measures and ratings of in-home functioning gathered through an Occupational Therapy evaluation.

Investigator: Anil K. Nair, MD
Project Title: Risk Evaluation and Disclosure in Mild Cognitive Impairment (RED-MCI)

The purpose of this project is to produce risk curves for estimating conversion from mild cognitive impairment (MCI) to Alzheimers Disease (AD) using APOE genotype and other risk factors using data from the ADCS Memory Impaiment Trial. The project will then conduct a pilot study of the effects of risk disclosure in MCI subjects and Controls selected from the ADC on measures of depression and anxiety.