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Novel Strategies for Blood-based Biomarkers for AD: Role of Genetic Variation in a Multivariate Framework

Award Number: R03AG050856
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2015
PERIOD OF PERFORMANCE END DATE: 04/30/2019

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Novel Strategies for Blood-based Biomarkers for AD: Role of Genetic Variation in a Multivariate Framework - DESCRIPTION (provided by applicant): Without any successful drug trials for Alzheimer's disease (AD) treatment and proven efficient therapies for AD, early detection of AD in asymptomatic or prodromal stages is critically important in order to increase chances of reducing irreversible brain damages, slowing down disease progression, and producing better results in any intervention trials. Several biomarkers from MRI, PET, CSF, and peripheral blood show their potential as diagnostic, prognostic, or therapeutic response biomarkers. Among them, blood-based biomarkers, especially proteomic analytes from peripheral blood have great potential as AD screening tools due to its minimal invasiveness and easy access of collection method and would have an extraordinary impact on research and eventually clinical care to facilitate the investigation of early intervention. During the last couple of years, many studies have been performed to investigate the direct relationship between a set of measured plasma (serum) proteomics analyte levels and a set of AD relevant phenotypes using various assay technologies. Due to several technical challenges related to sample collection, storage and assay, previous studies couldn't fully investigate the potential of plasma proteomics data, resulting in relatively weak replications. Beyond these technical issues, previous studies to date overlooked two very important factors: influence of genetic variations associated with each protein analyte and correlational structure of multi-analyte proteomic data. Recently we have shown that genetic variation substantially influences plasma proteomic analyte levels independent of disease status. Therefore, in assessing the diagnostic and prognostic significance of proteomic data, gene variants should be taken into account. Another potential reason of weak replication could be relative weak diagnostic power of individual analytes because the majority of investigation focused on the effect of each measured protein analyte level on a set of given phenotype. In many cases, multianalyte molecular biomarkers are correlated with one another and most of studies using plasma proteomics analytes did not consider correlational structure among analytes when assessing their diagnostic potential. Although the diagnostic power of individual analyte can be weak, multivariate approaches to identify a set of biologically meaningful ensembles of analytes may better elucidate diagnostic and prognostic power of plasma proteomic signature. In this proposed study, we will address these two knowledge gaps in assessing potential of plasma proteomic analytes through a multivariate approach by applying advanced analytic methods including multi-dimensional data reduction, gene pathway-enrichment analysis, imaging genetics, and supervised and unsupervised learning. Results of this project could have a transformative impact on identification and evaluation strategies of proteomic analytes as diagnostic, prognostic, or therapeutic response biomarkers and proposed advanced analytical strategies can be applied to fluid-based multi-analyte data for various neurodegenerative disorders in addition to AD.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2016	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	7060 STATE ROUTE 104	OSWEGO	NY	13126	OSWEGO	USA	Aging Research	000	3	2/9/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2016	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	7060 STATE ROUTE 104	OSWEGO	NY	13126	OSWEGO	USA	Aging Research	000	3	5/2/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Aging Research	000	2	1/12/2017	NON-COMPETING CONTINUATION	-$78,000
2017	2016	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	7060 STATE ROUTE 104	OSWEGO	NY	13126	OSWEGO	USA	Aging Research	003	3	3/1/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$17,299
2017	2016	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	7060 STATE ROUTE 104	OSWEGO	NY	13126	OSWEGO	USA	Aging Research	001	3	1/12/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$78,000
2017	2015	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Aging Research	002	1	3/1/2017	NEW	-$17,299
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $78,000 )
2016	2016	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Aging Research	000	2	4/22/2016	NON-COMPETING CONTINUATION	$78,000
														Subtotal = $78,000

Issue Date FY: 2015 ( Subtotal = $78,000 )
2015	2015	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Aging Research	000	1	8/31/2015	NEW	$78,000
														Subtotal = $78,000

Grand Total All Awards = $156,000

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Novel Strategies for Blood-based Biomarkers for AD: Role of Genetic Variation in a Multivariate Framework

Award Number: R03AG050856

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2015

PERIOD OF PERFORMANCE END DATE: 04/30/2019

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