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Changes in monocyte small noncoding RNAs as a predictor of cognitive decline in mild cognitive impairment and Alzheimer's disease

Award Number: R21AG081480
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Changes in monocyte small noncoding RNAs as a predictor of cognitive decline in mild cognitive impairment and Alzheimer's disease - ABSTRACT Twenty years after 9/11, the World Trade Center (WTC) responders show elevated rates mild cognitive impairment (MCI), an early sign of Alzheimer’s disease (AD) or AD-related dementia (ADRD). MCI is often regarded as an intermediate stage between normal aging and dementia; thus it provides a window of opportunity to understand the pathogenesis of the disorder and identify factors that lead to the conversion of MCI to dementia. Epigenetic vulnerability and gene-environment interactions have been implicated in the etiology of ADRD. In particular, small noncoding RNAs (sncRNAs) have been shown to be promising biomarkers and provide insights into its pathophysiology. Preliminary findings further revealed that monocyte subpopulation showed the largest changes in transcriptome associated with MCI; in line with evidence that monocytes play a pivotal role in mediating the interface between central and peripheral systems via transduction through the blood brain barrier. Despite this, there is no study which has investigated the epigenetic regulation by sncRNAs in monocyte subpopulation that may explain how these changes affect downstream gene expression and proteins associated with AD neuropathy and disease progression. This proposal builds on the preliminary findings in monocyte transcriptome and capitalizes on existing biobank and clinical data by evaluating monocyte sncRNA via smRNA-seq in a subset of 100 responders over a 24-month period. The proposed study will determine if changes in monocyte sncRNAs are associated with changes in clinical phenotype; and identify the gene targets of sncRNAs in monocyte subpopulation associated with cerebral neuropathology. To enhance the impact of this study, an exploratory aim is included to identify a multi-omic signature by integrating monocyte sncRNAs, mRNAs and plasma proteins that predicts changes in clinical phenotype. This study would be the first to examine the synergy between monocyte sncRNAs, mRNAs and plasma proteins in individuals converting to dementia. Findings from this study will shed light on regulation of monocyte responses in disease progression, help identify novel blood-based biomarkers that may inform treatment efforts.


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: 2024 ( Subtotal = $159,500 )
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Aging Research	001	2	2/23/2024	NON-COMPETING CONTINUATION	$143,550
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Aging Research	002	2	6/28/2024	NON-COMPETING CONTINUATION	$15,950
2024	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Aging Research	000	1	11/20/2023	NEW	$0
														Subtotal = $159,500

Issue Date FY: 2023 ( Subtotal = $279,125 )
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Aging Research	000	1	5/10/2023	NEW	$279,125
														Subtotal = $279,125

Grand Total All Awards = $438,625

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Changes in monocyte small noncoding RNAs as a predictor of cognitive decline in mild cognitive impairment and Alzheimer's disease

Award Number: R21AG081480

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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