HTORR Ocular Tissue Resource for Alzheimer's Disease Research

National Disease Research Interchange, Philadelphia PA

Investigators

Linked publications & trials

Abstract

Program Director/Principal Investigator (Bell, Thomas, J.): Project Summary: The development of effective diagnostics, treatments or cures for a wide range of diseases requires translational studies that are directly relevant to human pathophysiology. The use of human biospecimens plays a key role in accelerating scientific discoveries across the entire spectrum of biomedical research, including neurodegenerative diseases such as Alzheimer's disease and related dementias (AD/ADRD). Evidence from clinical trials suggests that preclinical interventions may be key to slowing AD/ADRD disease progression (Dehghani et al, 2018). However, this treatment strategy requires early detection, which highlights the need for improved diagnostics for AD/ADRD. While much progress has been made with brain imaging and blood-based biomarkers, the detection methods remain invasive and expensive. Ocular-based pathological changes represent a potential target for biomarker investigation. To further investigate the ocular pathogenesis in AD/ADRD, investigators require access to a unique human tissue resource that could provide rigorous, reproducible, and uniform collection of human ocular and neurological tissue from defined cohorts of healthy and AD/ADRD donors. Access to such a resource would be critical to ensuring consistent, predictive, and reproducible experimental results that could be translated to the clinic for AD/ADRD patients. The National Disease Research Interchange (NDRI) is a 501(c)(3), not-for-profit organization that remains at the forefront of coordinating biospecimen procurement to match the needs of advancing scientific experimental methodologies, and enabling cutting-edge research. For over 30 years, NDRI has received NIH funding for the parent award to this administrative supplement, the Human Tissue and Organs for Research Resource (HTORR) Grant Number: U42OD011158. NDRI is applying for the NOT-AG-20-034, Notice of Special Interest (NOSI) to expand its focus beyond the scope of HTORR to develop and implement the Ocular Tissue Resource for AD/ADRD Research (OTR-AD). For the current proposal to develop and implement the OTR-AD, NDRI will: 1) work with investigators and key stakeholders at NEI to identify high-priority ocular biospecimen needs to support AD/ADRD research, 2) screen, authorize, recover, and process ocular and other neurological biospecimens from eligible post mortem donors, and 3) distribute biospecimens to approved investigators and promote awareness of OTR-AD to recruit new investigators. In doing so, the biospecimen collection and preservation methods will be optimized to the experimental hypotheses and procedures for each ADBR study using NDRI's experience in coordinating standardized procurement, processing, preservation and shipping methods and maintaining industry best practices and standards regarding the donation of human tissue for research. The overall objective of the OTR-AD is to provide well-annotated ocular and neurological tissue from defined cohorts of healthy and AD/ADRD donors that are suitable to generate high-quality, reproducible data for scientific review and publication to meet the needs of investigators and support the advancement of AD/ADRD research. Relevance: As the most common cause of dementia, AD is a devastating, progressive neurodegenerative disease that affects an estimated 5.8 million Americans age 65 and over (Alzheimer's Association et al, 2020) and has a significant burden on the US healthcare system as well as caregivers. As of yet, there are no disease- modifying treatment options available for AD/ADRD patients, making this a high priority for the research community. Disappointing clinical trial results evaluating potential disease-modifying treatments in patients with AD/ADRD have shifted the therapeutic focus to preclinical intervention (Crous-Bou et al, 2017), which requires improved diagnostics. While significant advances continue to be made with the identification of blood-based biomarkers for AD/ADRD, a parallel approach could be the use of ocular imaging or other ocular biomarkers for early detection. The objective of this proposal is to provide ocular biospecimens from post mortem AD/ADRD donors, as well as non-diseased control donors for the Ocular Tissue Resource for AD/ADRD Research (OTR- AD) that are suitable to support critical lines of investigation that address key issues related to ocular pathogenesis in the disease. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page