Alzheimer's disease (AD) will become a public health crisis within the next 2-3 decades if left unchecked. There are no proven treatments that delay the onset or prevent the progression of AD, although several promising candidates are being developed. During the development of these therapies, it will be very important to have biomarkers that can identify individuals at high risk for AD in eariiest clinical stages in order to target them for clinical trials of disease-modifying therapies and to monitor therapy success. Clinicopathologic evidence suggests that AD pathology (particularly the buildup of amyloid plaques) begins 10-20 years before the onset of cognitive symptoms. The earliest clinical symptoms of AD are accompanied by, and likely due to, neuronal and synaptic dysfunction and/or cell death. Thus, it will be critical to identify individuals with """"""""preclinical"""""""" and very early stage symptomatic AD, prior to marked clinical symptoms and neuron loss, so new therapies will have the greatest chance to preserve normal brain function. The Adult Children Study (ACS) Biomarker Core was initially funded as a competitive supplement to the ACS PPG in April 2008. The Core's mission is to facilitate and support antecedent AD biomarkers research by providing the necessary infrastructure for the collection, storage, and dissemination of fluid (CSF and plasma) samples (and associated data) for our own research at Washington University and that of the greater AD scientific community. Since inception of the Core, our productivity has roughly doubled (as defined by the number of CSF and plasma samples collected, the number of samples disseminated to investigators, and the number of papers using our samples that have been published in peer-reviewed journals). Thus, in the present renewal application, we propose to build upon our success and propose the following aims:
Aim 1 : Maintain and grow a repository of fasted CSF and plasma samples for present and future aging and AD biomarker studies.
Aim 2 : Coordinate the distribution of CSF and plasma samples to qualified investigators.
Aim 3 : Compare the values obtained for CSF Ap42, tau and ptauiei in Project 2 as a function of assay (Innotest vs. xMAP) and plasma Ap species (APi^o, APx-40, APi.42. APx^2) as a function of fasting state.

Public Health Relevance

There are currently no effective treatments that will prevent Alzheimer's disease, halt its progression or delay its onset, although several therapeutic approaches are being developed and tested in clinical trials. Parallel efforts are being channeled into developing biomarkers that would aid in disease diagnosis and prognosis and assessing disease risk. Together these combined endeavors have the potential to provide physicians the tools to effectively diagnose and treat the disease, preferably everi before the onset of cognitive decline.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG026276-09
Application #
8732591
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
9
Fiscal Year
2014
Total Cost
$300,890
Indirect Cost
$102,936
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Schultz, Stephanie A; Gordon, Brian A; Mishra, Shruti et al. (2018) Widespread distribution of tauopathy in preclinical Alzheimer's disease. Neurobiol Aging 72:177-185
Schindler, Suzanne E; Gray, Julia D; Gordon, Brian A et al. (2018) Cerebrospinal fluid biomarkers measured by Elecsys assays compared to amyloid imaging. Alzheimers Dement 14:1460-1469
Javaherian, Kavon; Newman, Brianne M; Weng, Hua et al. (2018) Examining the Complicated Relationship Between Depressive Symptoms and Cognitive Impairment in Preclinical Alzheimer Disease. Alzheimer Dis Assoc Disord :
Weintraub, Sandra; Besser, Lilah; Dodge, Hiroko H et al. (2018) Version 3 of the Alzheimer Disease Centers' Neuropsychological Test Battery in the Uniform Data Set (UDS). Alzheimer Dis Assoc Disord 32:10-17
Jansen, Willemijn J; Ossenkoppele, Rik; Tijms, Betty M et al. (2018) Association of Cerebral Amyloid-? Aggregation With Cognitive Functioning in Persons Without Dementia. JAMA Psychiatry 75:84-95
Lucey, Brendan P; Hicks, Terry J; McLeland, Jennifer S et al. (2018) Effect of sleep on overnight cerebrospinal fluid amyloid ? kinetics. Ann Neurol 83:197-204
Islam, Jyoti; Zhang, Yanqing (2018) Brain MRI analysis for Alzheimer's disease diagnosis using an ensemble system of deep convolutional neural networks. Brain Inform 5:2
Gyurkovics, Mate; Balota, David A; Jackson, Jonathan D (2018) Mind-wandering in healthy aging and early stage Alzheimer's disease. Neuropsychology 32:89-101
Roe, Catherine M; Ances, Beau M; Head, Denise et al. (2018) Incident cognitive impairment: longitudinal changes in molecular, structural and cognitive biomarkers. Brain 141:3233-3248
Ihara, Ryoko; Vincent, Benjamin D; Baxter, Michael R et al. (2018) Relative neuron loss in hippocampal sclerosis of aging and Alzheimer's disease. Ann Neurol 84:741-753

Showing the most recent 10 out of 352 publications