Request for Information (RFI): Well Characterized Brain Bank Resources for Alzheimer's Disease-Related Dementias (ADRD) PET Ligand development and Cryo-EM Structural Analysis of Protein Species.

Notice Number: NOT-NS-18-018

Key Dates
Release Date: November 30, 2017

Related Announcements
None

Issued by
National Institute of Neurological Disorders and Stroke (NINDS)

Purpose

The National Institute of Neurological Disorders and Stroke (NINDS) seeks brain tissue resource information for new ADRD initiatives that will focus on the development of PET ligands for Alzheimer’s Disease Related Dementias (ADRDs) and Cryo-Electron Microscopy (Cryo-EM) structural analysis of protein species related to ADRD pathogenesis. Resources identified through this RFI will be posted on the NINDS Resource webpage and investigators applying to the new ADRD initiatives will be encouraged to integrate these resources through collaborations into their research plan.

Background  

In 2016, NINDS organized a conference on Alzheimer's Disease Related Dementias (ADRDs) which focused on  frontotemporal degeneration (FTD), Lewy body dementias (LBD) (including dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), vascular contributions to cognitive impairment and dementia (VCID), mixed diseases including the associated diagnostic challenges of multiple etiology dementias (MED), and issues related to health disparities. The conference complemented the National Institute on Aging’s “Alzheimer’s Disease Research Summit 2015: Path to Treatment and Prevention.” Both conferences responded to the National Alzheimer’s Project Act that was signed into law in January 2011. The objective of the ADRD conference was to contribute to the efforts directed at preventing and effectively treating Alzheimer’s disease, including Alzheimer’s disease-related dementias, by 2025.  The Alzheimer’s Disease-Related Dementias steering committee solicited input from internationally recognized experts to develop prioritized recommendations to guide scientific research in the next 5 to 10 years.  Cross-cutting recommendations from the ADRD working groups focused on basic science and biomarker developments that can further our understanding of protein species associated with ADRD pathogenesis, as well as to advance tool development.  Biomarker development is crucial for patient stratification and disease progression. 

Although recent advances in Tau PET ligand development look promising for Alzheimer’s disease, specificity and selectivity of PET ligands for non-AD tauopathies has not yet been achieved and PET ligands for alpha-synuclein and TDP43 are still elusive. To accelerate the development and characterization of PET ligands and structural analyses of ADRD protein species related to disease pathogenesis, NINDS requests information on human postmortem (or biopsy) brain tissue that would be available for sharing with the research community.  Tissue to be shared would ideally be linked to de-identified clinical data (e.g., neurological, neuropsychological and neuroimaging data) for the development of these tools and resources.  Typically, several grams of tissue depending on the pathogenic protein load and brain region are needed for these studies.

Information Requested

NINDS invites researchers, clinicians and programs with collections of well characterized brain tissue and interested in the development of collaborations for FY18 ADRD Funding Opportunity Announcements (FOAs) to submit information on brain tissue and associated de-identified clinical data availability.

Key information regarding brain tissue collections and associated de-identified clinical data available for PET ligand development and protein structural analysis would include:

  • Average post-mortem interval (10-76 hours desirable), and available measures of tissue quality (e.g., tissue pH or RIN)
  • Availability of frozen tissue (number of brains), average amount of tissue available for sharing with respect to brain region(s) is provided;
  • Method of freezing (e.g., flash frozen)
  • Indication of availability of corresponding fixed tissue (including nature and duration of fixation and methods of storing fixed tissue (e.g., cryo-preservation);
  • Antemortem clinical diagnosis, age at diagnosis, age at death, sex, ethnicity:
  • Number of brains with genetic characterization – family history of related neurologic diseases, known causative and risk gene mutations, common genetic risk factors (e.g., APOE, MAPT, GBA, GRN, C9ORF72, SCNA, etc.), availability of whole exome or genome data; and/or data on genome-wide significant risk factors;
  • Pathological characterization of primary and associated disease processes using consensus neuropathological criteria for ADRD.
  • Diagnostic criteria used
  • Examples of past sharing of the resource
  • Requirements for resource sharing e.g. MOU, MTA and any key restrictions
  • Name of individual and email contact for the brain tissue resource.

How to Submit a Response

Response to this RFI must be submitted to ADRDTissueResources@ninds.nih.gov by January 15th, 2017]. Responses should be provided in a narrative with links to pertinent supplemental information if needed. No attachments will be accepted. No proprietary, classified, confidential, or sensitive information should be included in your response

Responses to this RFI are voluntary. This RFI seeks input for planning purposes only and should not be construed as a solicitation for applications or an obligation on the part of the Federal Government, the National Institutes of Health, or individual NIH Institutes or Centers. The information collected will not be considered confidential. Processed results may be shared internally or with members of health-related scientific work groups, and will be posted on the NINDS Resource webpage, as appropriate.  The NIH acknowledges receipt of information submitted, but will not comment on the content.  

Inquiries

Please direct all inquiries to:

Margaret Sutherland, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5680
Email:sutherlandm@ninds.nih.gov