This application seeks a renewal of NIA T32 AG00258 entitled """"""""Neurobehavior, Neuroendocrinology, and Genetics of AD"""""""". By the end of our second funding cycle our program will have supported 27 post-doctoral trainees (12 with M.D. degrees, 3 of whom also have PhDs, and 15 with Ph.D. degrees). Our training efforts have been successful, as evidenced by the accomplishments of our trainees, as well as by our ability to attract qualified candidates and physician trainees to our program. In the next funding cycle, we will continue to provide post-doctoral training in clinical research regarding the neurobehavior, neuroendocrinology, and neurogenetics of Alzheimer's disease (AD) and related dementias. In particular, the program will focus on training clinical researchers capable of translating critical findings from basic science into hypotheses regarding the etiology, pathophysiology, and treatment of AD. Furthermore, clinical researchers will receive specialized training in two areas of study, neuroendocrinology and neurogenetics, that hold promise for increasing our understanding of the pathogenesis of AD and for developing new therapeutic approaches. These areas are not typically emphasized in graduate training of psychiatrists, neurologists, or neuropsychologists. However, recent advances have underscored the importance of genetic factors such as amyloid precursor protein and presenilin mutations, and apolipoprotein e genotype. Neuroendocrine factors such as disruptions of lipid, insulin and glucose metabolism, inflammation, and glucocorticoid status may also play an important pathogeneticjole in modifying the effects of AD susceptibility genes, thereby affecting the neuropsychologic expression of AD. Clinical investigators capable of bridging the fields of neurogenetics, neuropsychology, and neuroendocrinology will be needed to disentangle and define these potentially critical interactions. The program is supported by the rich and interactive research environment of the University of Washington and Veterans Affairs Puget Sound Health Care System, where a critical mass of faculty conduct both basic science and clinical research in the neuroendocrinology and neurogenetics of AD. The ADRC at the UWwill also serve as a resource for faculty and trainees. Although there is a long-standing commitment to aging training at our institution, our proposed program is unique in its interdisciplinary nature and focus on clinical translational research in AD and related conditions. As such, it will provide a much-needed approach to the training of clinical research scientists whose work will address these complex disorders.

Public Health Relevance

Our program trains researchers who are able to translate findings from basic science into clinical models of Alzheimer's disease and other dementias, and thereby facilitate the development of new treatments for these challenging diseases. In particular, the program focuses on the interactive role played by genetic and metabolic factors such as diabetes and stress in increasing the risk of dementia. These factors are highly prevalent in our society, and a better understanding of their role may lead to new treatments and strategies for preventing dementia or delaying its onset.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Institutional National Research Service Award (T32)
Project #
5T32AG000258-14
Application #
8245044
Study Section
Special Emphasis Panel (ZAG1-ZIJ-7 (J4))
Program Officer
Silverberg, Nina B
Project Start
1999-06-15
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
14
Fiscal Year
2012
Total Cost
$387,765
Indirect Cost
$31,027
Name
University of Washington
Department
Psychiatry
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Melief, E J; Gibbs, J T; Li, X et al. (2016) Characterization of cognitive impairments and neurotransmitter changes in a novel transgenic mouse lacking Slc10a4. Neuroscience 324:399-406
Meabon, James S; de Laat, Rian; Ieguchi, Katsuaki et al. (2016) Intracellular LINGO-1 negatively regulates Trk neurotrophin receptor signaling. Mol Cell Neurosci 70:1-10
Huber, B R; Meabon, J S; Hoffer, Z S et al. (2016) Blast exposure causes dynamic microglial/macrophage responses and microdomains of brain microvessel dysfunction. Neuroscience 319:206-20
Meabon, James S; Huber, Bertrand R; Cross, Donna J et al. (2016) Repetitive blast exposure in mice and combat veterans causes persistent cerebellar dysfunction. Sci Transl Med 8:321ra6
Hanson, Angela J; Banks, William A; Hernandez Saucedo, Hector et al. (2016) Apolipoprotein E Genotype and Sex Influence Glucose Tolerance in Older Adults: A Cross-Sectional Study. Dement Geriatr Cogn Dis Extra 6:78-89
Melief, Erica J; Cudaback, Eiron; Jorstad, Nikolas L et al. (2015) Partial depletion of striatal dopamine enhances penetrance of cognitive deficits in a transgenic mouse model of Alzheimer's disease. J Neurosci Res 93:1413-22
Gross, Alden L; Benitez, Andreana; Shih, Regina et al. (2015) Predictors of Retest Effects in a Longitudinal Study of Cognitive Aging in a Diverse Community-Based Sample. J Int Neuropsychol Soc 21:506-18
Foraker, Jessica; Millard, Steven P; Leong, Lesley et al. (2015) The APOE Gene is Differentially Methylated in Alzheimer's Disease. J Alzheimers Dis 48:745-55
Morgan, R Garrett; Gibbs, Jeffrey T; Melief, Erica J et al. (2015) Relative contributions of severe dopaminergic neuron ablation and dopamine depletion to cognitive impairment. Exp Neurol 271:205-14
Hanson, Angela J; Bayer, Jennifer L; Baker, Laura D et al. (2015) Differential Effects of Meal Challenges on Cognition, Metabolism, and Biomarkers for Apolipoprotein E ɛ4 Carriers and Adults with Mild Cognitive Impairment. J Alzheimers Dis 48:205-18

Showing the most recent 10 out of 65 publications