Contact Points
Nashville, TN 37232-0011
No source other than Vanderbilt University Medical Center's Timothy Hohman, Ph.D. Assistant Professor of Neurology, can meet the requirements of this contract. Familiarity with BLSA cognitive and imaging data are required for continuity of analytic approaches for cognitive and imaging data, as well as expertise with the novel proposed analytic methods. Dr. Hohman is uniquely qualified because he has worked extensively with BLSA imaging and cognitive data while a predoctoral fellow in BABS and he is expert in the application of the proposed novel PrediXcan approach.
The National Institute on Aging (NIA) Laboratory of Behavioral Neuroscience’s (LBN) main objective of the requirement is to investigate sex differences in genetic risk scores in the BLSA in relation to newly acquired plasma biomarkers of AD pathology and neurodegeneration. The outcome of this work will highlight sex dimorphic AD and neurodegeneration pathways that drive cognitive and brain aging.
The purpose of the overall program of research in the Laboratory of Behavioral Neuroscience (LBN) is to enhance our understanding of age-associated physical and biological changes in health and disease. The Brain Aging and Behavior Section (BABS) investigates structural and functional brain changes and how they relate to age-associated changes in cognition, including the development of Alzheimer’s disease (AD), and factors that modify cognitive and brain aging. Given that women have a higher prevalence of AD, BABS investigators are particularly interested in potential sex differences in brain and cognitive aging. Recently, they found that men actually had steeper rates of cognitive decline in some cognitive functions and that there were no cognitive functions for which women showed steeper decline. These findings highlight the importance of further investigation of sex differences in associations of biomarkers of preclinical AD during the earliest stages of the disease process with brain and cognitive aging.
Recent work has identified a sex difference in the association between CSF and pathology-based biomarkers of Alzheimer’s disease neuropathology and longitudinal changes in brain structure and cognitive function (Koran et al., 2016). Moderating effects of the APOE genotype on the observed sex differences were also observed, suggesting that there may be unique molecular drivers of cognitive decline and neurodegeneration in males and females.
Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work below:
This current requirement will involve first, replicating sex differences in the association between AD biomarkers and brain aging outcomes using newly acquired plasma biomarker data (Aβ40, Aβ42, GFAP, NF-L) from the Baltimore Longitudinal Study of Aging. Sex interactions of genetic predictors of plasma biomarkers on longitudinal cognition and brain volumes will be investigated. Second, analyses will be performed to investigate sex-specific genomic drivers of cognitive impairment in the presence of enhanced biomarkers of AD and neurodegeneration.
The Contractor is to perform the following requirements:
- Extend prior work by using newly acquired plasma biomarkers of AD pathology and neurodegeneration in the the Baltimore Longitudinal Study of Aging (BLSA) to investigate sex dfiferences in genetic predictors of AD and neurodegeneration in relation to brain and cognitive aging. The Contractor will first use plasma biomarkers to replicate prior findings of sex differences in genetic risk in relation to amyloid and tau pathology based on CSF biomarkers and neuropathology studies.
- Extend investigations of genetic risk to examine potential sex differences in the genetic risk profiles underlying age-associated changes in Neurofilament light (NF-L) and GFAP.
- Perform analyses to investigate sex-specific genomic drivers of cognitive and brain aging in the presence of enhanced AD and neurodegeneration biomarkers. This analysis will require a classic genome-wide association analysis approach in combination with an innovative predicted gene-expression analysis called PrediXcan (Gamzon et al, 2015). Use the PrediXcan approach to build SNP prediction models for tissue-specific gene expression levels and “impute” gene expression levels based on genotype.
GOVERNMENT RESPONSIBILITIES
Provide plasma biomarkers data and imaging data, as well as other necessary information, including diagnostic data, for analysis of genetic data in relation to biomarkers, brain volumes, cognition and affect. All data will be de-identified.
DELIVERY OR DELIVERABLES
Planned Deliverables:
1) Tissue-specific predicted gene expression profiles in BLSA.
2) Replication of sex and APOE interactions with plasma biomarkers of AD and neurodegenertation on longitudinal brain aging outcomes.
3) Preparation of a novel report on sex-specific molecular drivers of the relation between specified plasma biomarkers and cognitive decline,.
REPORTING REQUIREMENTS
12 months from the start of project:
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- Reports in manuscript format describing results of each of the deliverables.
- Excel spreadsheet with gene expression profiles.
KEY PERSONNEL:
Cognitive neuroscientist and computational geneticist.
DATA RIGHTS:
The National Institute on Aging shall have unlimited rights to and ownership of all deliverables provided under this contract including reports, recommendations, briefings, work plans and all other deliverables. This includes the deliverables provided under the basic contract and any optional task deliverables exercised by the contracting officer. In addition, it includes any additional deliverables required by contract change. The definition of “unlimited rights” is contained in Federal Acquisition Regulation (FAR) 27.401, “Definitions.” FAR clause 52.227-14, “Rights in Data-General, ” is hereby incorporated by reference and made a part of this contract/order.
Contract Type:
A Firm Fixed Price type order award not exceeding the Simplified Acquisition Threshold is anticipated to be awarded resulting from this requirement.
Summary Statement:
The Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size must be included in the response.
All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov.”
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The following provisions and clauses apply to this acquisition and are incorporated as an attachment. Offerors MUST complete the provision at 52.204-24 and 52.204-26 and submit completed copies as separate documents with their quotation.
1. FAR 52.204-24, Representation Regarding Certain Telecommunications and Video Surveillance Services or Equipment (Oct 2020)
2. FAR 52.204-25, Prohibition on Contracting for Certain Telecommunications and Video Surveillance Services or Equipment (Aug 2020)
3. FAR 52.204-26, Covered Telecommunications Equipment or Services-Representation (Oct 2020)
Interested parties may identify in writing their interest and capability in response to this requirement. Responses to this notice shall contain sufficient information to establish the interested parties’ bona-fide capabilities for fulfilling the requirement and include: unit price, list price, shipping and handling costs, the delivery period after contract award, the prompt payment discount terms, the F.O.B. Point (Destination or Origin), the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size. All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov.
All responses must be received by closing date and must reference the announcement. Responses may be submitted electronically to the attention of the contract specialist. Fax responses will not be accepted.
All responsible sources may submit a bid, proposal, or quotation which shall be considered by the agency.