Neurobehavior, Neuroendocrinology, and Genetics of AD

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”。到我们的第一个资助周期结束时，我们的计划将支持12名博士后实习生(6名拥有医学博士学位，6名拥有博士学位)。我们的首批培训工作取得了成功，我们的实习生取得了成就，我们有能力吸引合格的少数族裔候选人和医生实习生加入我们的计划。鉴于我们最初的成功，以及对实习生支持需求的增加，我们要求将我们的计划从5个实习生职位扩大到7个。 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阿尔茨海默病发病机制的了解，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，如脂质和胰岛素代谢紊乱、炎症和糖皮质激素状态，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的致病作用。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。

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 first funding cycle our program will have supported 12 post-doctoral trainees (6 with M.D. degrees and 6 with Ph.D. degrees). Our inaugural training efforts have been successful, as evidenced by the accomplishments of our trainees, as well as by our ability to attract qualified minority candidates and physician trainees to our program. Given our initial success, and the increase in demand for trainee support, we request an expansion of our program from five to seven trainee positions. 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 and insulin metabolism, inflammation, and glucocorticoid status may also play an important pathogenetic role 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 neuroendocrinotogy 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 UW will 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.