Neurobehavior, Neuroendocrinology, and Genetics of AD

AD 的神经行为、神经内分泌学和遗传学

• 批准号: 8060551
• 负责人: SUZANNE CRAFT
• 金额: $ 43.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-15 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8060551
• 关键词: Genetic; Neuroendocrinology; neurobehavior

DESCRIPTION (provided by applicant): 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. 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.

描述(由申请人提供)：本申请寻求续期NIA T32 AG00258，标题为“AD的神经行为、神经内分泌学和遗传学”。到我们的第二个资助周期结束时，我们的计划将支持27名博士后实习生(12名拥有医学博士学位，其中3名还拥有博士学位，15名拥有博士学位)。我们的培训工作取得了成功，我们的学员取得了成就，我们有能力吸引合格的候选人和医生学员加入我们的项目，这就是明证。在下一个资助周期，我们将继续提供有关阿尔茨海默病(AD)和相关痴呆的神经行为、神经内分泌学和神经遗传学的临床研究的博士后培训。特别是，该计划将侧重于培训临床研究人员，他们能够将基础科学的关键发现转化为关于AD的病因、病理生理学和治疗的假说。此外，临床研究人员将接受神经内分泌学和神经遗传学这两个研究领域的专门培训，这两个领域有望增加我们对AD发病机制的了解，并开发新的治疗方法。在精神病学家、神经病学家或神经心理学家的研究生培训中，这些领域通常不被强调。然而，最近的进展强调了遗传因素的重要性，如淀粉样前体蛋白和早老素突变，以及载脂蛋白e基因。神经内分泌因素，如脂质、胰岛素和葡萄糖代谢紊乱、炎症和糖皮质激素状态等，也可能在改变AD易感基因的作用，从而影响AD的神经心理表达方面发挥重要作用。需要能够连接神经遗传学、神经心理学和神经内分泌学领域的临床研究人员来理清和界定这些潜在的关键相互作用。该计划得到了华盛顿大学和普吉特退伍军人事务部健全的医疗保健系统丰富和互动的研究环境的支持，在那里，关键的教职员工在AD的神经内分泌学和神经遗传学方面进行基础科学和临床研究。华盛顿大学的ADRC也将作为教职员工和实习生的资源。尽管我们机构长期以来一直致力于老龄培训，但我们提议的项目在跨学科性质上是独一无二的，并专注于AD和相关疾病的临床翻译研究。因此，它将提供一种急需的方法来培训临床研究科学家，他们的工作将解决这些复杂的疾病。 相关性：我们的计划培训能够将基础科学的研究成果转化为阿尔茨海默病和其他痴呆症的临床模型的研究人员，从而促进这些具有挑战性的疾病的新疗法的开发。该计划尤其关注糖尿病和压力等遗传和新陈代谢因素在增加痴呆症风险方面所起的交互作用。这些因素在我们的社会中非常普遍，更好地了解它们的作用可能会导致预防痴呆症或延缓其发病的新的治疗方法和策略。