NiAD Supplement WashU Start Up

NiAD 补充剂 WashU Start Up

• 批准号: 9934358
• 负责人: JOHN N. CONSTANTINO
• 金额: $ 23.73万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9934358
• 关键词: Address; Administrative Supplement; Adult; Affect; Age; Aging; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Appearance; Attention; Biochemical; Biological Markers; Cerebrospinal Fluid; Cessation of life; Chromosomes, Human, Pair 21; Clinical; Cognition; Cognitive; Collection; Complex; Consequentialism; Data; Dementia; Development; Down Syndrome; Elderly; Equilibrium; Esthesia; Evaluation; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Future; Gait; Gene Proteins; Genetic; Goals; Home environment; Image; Impaired cognition; Impairment; Individual; Inherited; Injury; Institutes; Institutionalization; Intellectual functioning disability; Late Onset Alzheimer Disease; Life; Link; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Modeling; Motor; National Institute of Child Health and Human Development; Nerve Degeneration; Nervous system structure; Neurofibrillary Tangles; Neurologic; Neuropsychology; Outcome; Participant; Pathology; Performance; Peripheral; Peripheral Nervous System; Phase; Plasma; Population; Positioning Attribute; Positron-Emission Tomography; Protein Precursors; Proteins; Proteomics; Protocols documentation; Request for Proposals; Research; Resources; Risk; Risk Factors; Role; Senile Plaques; Sensory; Severities; Site; Structure; Symptoms; Therapeutic; Therapeutic Trials; Training; Universities; Vision; Washington; Work; abeta deposition; cognitive function; cohort; combat; cost; design; disability; falls; functional decline; high risk; imaging biomarker; imaging genetics; molecular marker; neglect; neuroimaging; neuropathology; novel; performance site; pre-clinical; preclinical evaluation; premature; prevent; protective factors; recruit; response; tau Proteins; therapy design; treatment trial

NiAD Summary/Abstract: Individuals with Down syndrome (DS) have been largely neglected in therapeutic and biomarker studies of Alzheimer’s disease (AD). Adults with DS are uniformly affected by AD pathology by their 30’s and have a 70-80% chance of clinical dementia by their 60’s. In 95% of cases, DS is associated with three copies of chromosome 21, each containing of copy of the Amyloid-beta (Aβ) Precursor Protein gene (leading to a 1.5-fold increase in Aβ protein). Yet, nowhere is it clearer than in DS that Aβ deposition is not sufficient to produce dementia as individuals harbor this pathology for over a decade before cognitive decline is apparent. DS can be seen as a setting of amplified sensitivity to risk and protective factors that moderate the relationship between Aβ, neurodegeneration and clinical dementia. Understanding the factors that moderate this relationship in DS and biomarkers for those factors is critically important in the design of therapeutic trials for AD in DS and ingeneral. Thus, this longitudinal study of Neurodegeneration in Aging DS (NiAD) and its relationship to cognition has the potential to: 1) identify critical factors that link Aβ deposition to neurodegeneration and, ultimately, dementia; 2) define biomarkers for these factors; and, most importantly, 3) set a foundation for an efficient transition from this biomarker study to a therapeutic trial to combat AD in DS augmented by biomarker outcomes. For the past 5 years, the three independent research groups included in this application have been studying the course of Aβ deposition and other imaging biomarkers and their impact on cognitive/functional measures in adults with DS [(a) the combined Pittsburgh/Madison study; (b) the Banner Alzheimer’s Institute study; and (c) the Cambridge study]. In ongoing work, 140 adults with DS (including 23 with AD-dementia) have undergone magnetic resonance imaging (MRI) and amyloid-positron emission tomography (PET) scans and neuropsychological/functional assessments across these three studies. These research groups now propose to combine resources and harmonize all protocols in response to the request from NIA/NICHD to develop a large AD biomarker study in DS. This study will be further strengthened by aligning NiAD with the three largest ongoing longitudinal studies of AD biomarkers: the Alzheimer Disease Neuroimaging Initiative (ADNI), the Dominantly Inherited Alzheimer Network (DIAN) and the Alzheimer Prevention Initiative (API). All data will be made available in an open-access format using a model similar to ADNI. The established DS cohort is a significant advantage that will shorten the recruitment phase, maximize longitudinal data that can be acquired and allow for addition of new biomarkers to be compared to longitudinal clinical and imaging measures. The proposed 5-year longitudinal study will examine progression of AD related biomarkers (Aβ-, tau- and flurodeoxyglucose-PET, structural and functional MRI, cerebrospinal fluid Aβ and tau, plasma Aβ and proteomics, genetics, neuropathology) and cognitive/functional measures in 180 adults with DS (>25 yrs. of age) and 40 biomarker-controls. Subjects will be re-evaluated every 16 months to assess changes in cognition/adaptive functioning and at 32 months to detect biomarker changes.

NiAD总结/文摘:

项目成果

Integrating Biomarker Outcomes into Clinical Trials for Alzheimer's Disease in Down Syndrome.

• DOI: 10.14283/jpad.2020.35
• 发表时间: 2021
• 期刊: The journal of prevention of Alzheimer's disease
• 作者: Rafii MS;Zaman S;Handen BL
• 通讯作者: Handen BL

Relationship of amyloid beta and neurofibrillary tau deposition in Neurodegeneration in Aging Down Syndrome (NiAD) study at baseline.

• DOI: 10.1002/trc2.12096
• 发表时间: 2020
• 期刊: Alzheimer's & dementia (New York, N. Y.)
• 作者: Tudorascu DL;Laymon CM;Zammit M;Minhas DS;Anderson SJ;Ellison PA;Zaman S;Ances BM;Sabbagh M;Johnson SC;Mathis CA;Klunk WE;Handen BL;Christian BT;Cohen AD
• 通讯作者: Cohen AD