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: 8445198
• 负责人: Thomas J Montine
• 金额: $ 7.15万
• 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 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8445198
• 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）：本申请寻求更新NIA T32 AG00258，标题为“AD的神经行为，神经内分泌学和遗传学”。到第二个资助周期结束时，我们的项目将支持27名博士后学员（12名具有医学博士学位，3名同时具有博士学位，15名具有博士学位）。我们的培训工作是成功的，从我们的学员的成就，以及我们吸引合格的候选人和医生学员到我们的项目的能力证明了这一点。在下一个资助周期，我们将继续在阿尔茨海默病（AD）及相关痴呆的神经行为学、神经内分泌学和神经遗传学的临床研究方面提供博士后培训。特别是，该项目将重点培训临床研究人员，使他们能够将基础科学的重要发现转化为有关阿尔茨海默病病因学、病理生理学和治疗的假设。此外，临床研究人员将在神经内分泌学和神经遗传学两个研究领域接受专门培训，这有望增加我们对阿尔茨海默病发病机制的理解，并开发新的治疗方法。这些领域在精神科医生、神经学家或神经心理学家的研究生培训中通常不被强调。然而，最近的进展强调了遗传因素的重要性，如淀粉样蛋白前体蛋白和早老素突变，以及载脂蛋白e基因型。神经内分泌因素如脂质、胰岛素和糖代谢紊乱、炎症和糖皮质激素状态等也可能在改变AD易感基因的作用中发挥重要的致病作用，从而影响AD的神经心理表达。临床研究人员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，以解开和定义这些潜在的关键相互作用。该项目得到了华盛顿大学和退伍军人事务普吉特海湾医疗保健系统丰富而互动的研究环境的支持，在那里，大量的教师在阿尔茨海默病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。威斯康星大学的ADRC也将为教员和学员提供资源。虽然我们机构长期致力于衰老培训，但我们提议的项目在跨学科性质上是独一无二的，并专注于阿尔茨海默病及相关疾病的临床转化研究。因此，它将为临床研究科学家的培训提供急需的方法，这些科学家的工作将解决这些复杂的疾病。

项目成果

Characterization of cognitive impairments and neurotransmitter changes in a novel transgenic mouse lacking Slc10a4.

• DOI: 10.1016/j.neuroscience.2016.03.037
• 发表时间: 2016-06-02
• 期刊: Neuroscience
• 影响因子: 3.3
• 作者: Melief EJ;Gibbs JT;Li X;Morgan RG;Keene CD;Montine TJ;Palmiter RD;Darvas M
• 通讯作者: Darvas M

Delivery of therapeutic peptides and proteins to the CNS.

将治疗性肽和蛋白质递送至中枢神经系统。

• DOI: 10.1016/bs.apha.2014.06.004
• 发表时间: 2014
• 期刊: Advances in pharmacology (San Diego, Calif.)
• 作者: Salameh,ThereseS;Banks,WilliamA
• 通讯作者: Banks,WilliamA

Statin users without an APOE-epsilon4 allele have increased insulin resistance.

没有 APOE-epsilon4 等位基因的他汀类药物使用者会增加胰岛素抵抗。

• DOI: 10.3233/jad-2010-1319
• 发表时间: 2010
• 期刊: Journal of Alzheimer's disease : JAD
• 作者: VanFossen,BrianT;Watson,GStennis;Baker,LauraD;Rhoads,KristofferW;Cholerton,BrennaA;Reger,MarkA;Plymate,StephenR;Schellenberg,Gerald;Craft,Suzanne
• 通讯作者: Craft,Suzanne

Attention Network Test fMRI data for participants with Parkinson's disease and healthy elderly.

注意网络测试帕金森病参与者和健康老年人的功能磁共振成像数据。

• DOI: 10.12688/f1000research.19288.1
• 发表时间: 2019
• 期刊: F1000Research
• 作者: Day,TrevorKM;Madhyastha,TaraM;Askren,MaryK;Boord,Peter;Montine,ThomasJ;Grabowski,ThomasJ
• 通讯作者: Grabowski,ThomasJ

Sex and ApoE genotype differences in treatment response to two doses of intranasal insulin in adults with mild cognitive impairment or Alzheimer's disease.

• DOI: 10.3233/jad-122308
• 发表时间: 2013
• 期刊: Journal of Alzheimer's disease : JAD
• 作者: Claxton A;Baker LD;Wilkinson CW;Trittschuh EH;Chapman D;Watson GS;Cholerton B;Plymate SR;Arbuckle M;Craft S
• 通讯作者: Craft S