The search for genetic and environmental factors that may interact with the processes of advancing age to increase the incidence of Alzheimer's disease (AD) is an ongoing effort in many laboratories. Most of the efforts in discovering genetic factors associated with AD are centered on the nuclear genome. Yet, many studies have shown that mitochondrial structure and function change with both advancing age and, especially, with the onset and progression of AD. Investigators at the University of Kansas (KU) have been investigating the effects of cardiorespiratory fitness on AD progression and on the genetic and biochemical changes in brain mitochondria during the aging process and in AD. This combination of expertise and interests has led us to this proposed Core G, the Mitochondrial Genomics and Metabolism (MGM) Core. The goal of the MGM Core is to provide resources and expertise to investigators at KU and at other research institutions that will support studies on platelet, brain and muscle mitochondria obtained from well-characterized cases of AD, mild cognitive impairment (MCI), and age-matched controls. The scientific focus of the MGM Core is based on the idea that mitochondria play an important role in the pathogenesis of AD, both familial and late onset AD. The generation of reactive oxygen species in mitochondria, especially mitochondria with defective metabolism such as those in AD, can lead to oxidative modification of mtDNA, increases in the frequency of mutations in mtDNA, and mitochondrial dysfunction in terms of oxidative phosphorylation The Specific Aims of the MGM Core are: 1) Prepare, catalog, and store mitochondria, protein extracts, DNA, and RNA from living and deceased subjects recruited by the Clinical Core;2) Prepare and bank cybrid lines using neuronal cells and platelet mitochondria from living subjects;3) Perform limited mitochondrial DNA (mtDNA) sequence analysis and measurements of 8-OH-2-dG in order to jump-start larger, independently funded research into AD mtDNA gene structure and expression;and 4) Develop mitochondria- and metabolism-oriented AD research in the Kansas City region and assist in national AD research efforts focused on mitochondria.
The genetic factors that lead to the Alzheimer's disease state are still not fully defined. Mitochondrial abnormalities in structure and function may be a common mechanism underlying the appearance and progression of AD. Investigation of mitochondrial function is one of the main avenues of future research that will be conducted by investigators at the University of Kansas and other institutions.
|Burke, Shanna L; Maramaldi, Peter; Cadet, Tamara et al. (2018) Decreasing hazards of Alzheimer's disease with the use of antidepressants: mitigating the risk of depression and apolipoprotein E. Int J Geriatr Psychiatry 33:200-211|
|Menta, Blaise W; Swerdlow, Russell H (2018) An Integrative Overview of Non-Amyloid and Non-Tau Pathologies in Alzheimer's Disease. Neurochem Res :|
|Deng, Yue; Jiang, Beichen; Rankin, Carolyn L et al. (2018) Methionine sulfoxide reductase A (MsrA) mediates the ubiquitination of 14-3-3 protein isotypes in brain. Free Radic Biol Med 129:600-607|
|Ptomey, Lauren T; Szabo, Amanda N; Willis, Erik A et al. (2018) Remote Exercise for Adults with Down Syndrome. Transl J Am Coll Sports Med 3:60-65|
|Qian, Winnie; Fischer, Corinne E; Schweizer, Tom A et al. (2018) Association Between Psychosis Phenotype and APOE Genotype on the Clinical Profiles of Alzheimer's Disease. Curr Alzheimer Res 15:187-194|
|Perales, Jaime; Hinton, Ladson; Burns, Jeffrey et al. (2018) Cardiovascular health and cognitive function among Mexican older adults: cross-sectional results from the WHO Study on Global Ageing and Adult Health. Int Psychogeriatr 30:1827-1836|
|Gallagher, Damien; Kiss, Alex; Lanctot, Krista et al. (2018) Depression and Risk of Alzheimer Dementia: A Longitudinal Analysis to Determine Predictors of Increased Risk among Older Adults with Depression. Am J Geriatr Psychiatry 26:819-827|
|Perales, Jaime; Moore, W Todd; Fernandez, Cielo et al. (2018) Feasibility of an Alzheimer's disease knowledge intervention in the Latino community. Ethn Health :1-12|
|Haaksma, Miriam L; Calderón-Larrañaga, Amaia; Olde Rikkert, Marcel G M et al. (2018) Cognitive and functional progression in Alzheimer disease: A prediction model of latent classes. Int J Geriatr Psychiatry 33:1057-1064|
|Gupta, Aditi; Thomas, Tashra S; Klein, Jeffrey A et al. (2018) Discrepancies between Perceived and Measured Cognition in Kidney Transplant Recipients: Implications for Clinical Management. Nephron 138:22-28|
Showing the most recent 10 out of 333 publications