U24AG079683

Shared Resource to Develop Tools and Reagents to Study Structural Polymorphisms in Abeta Amyloid Aggregates in AD - Project Abstract

Alzheimer's Disease (AD) is currently an incurable neurodegenerative disease that affects over 35 million people worldwide, including 5.4 million individuals in the USA, with a new case diagnosed every minute. Amyloids occur commonly as key pathological features in a wide variety of neurodegenerative diseases such as AD. Despite 30 years of intensive research, important questions about the significance, mechanisms, and role in pathogenesis of amyloids remain unresolved.

Because of the strong implication of amyloid beta (Abeta) peptide in familial AD, preparations of amyloid aggregates (oligomers, fibrils) have been featured in over 100,000 publications over the past 30 years. However, in many cases, conflicting, contradictory, and non-reproducible data obfuscate the underlying mechanisms of pathogenesis.

Advances in structural biology have established the structures of several distinct types of amyloid, leading to the discovery that amyloid structures are highly polymorphic, with the same protein sequence adopting distinct beta sheet folds. Moreover, different structures seem to correlate with different disease subtypes, indicating that structural variation plays a role in pathogenesis. This polymorphism and structural heterogeneity may also underlie the irreproducibility and conflicting results that have plagued amyloid research.

This suggests a critical need for well-characterized, standardized protocols for the preparation of different types of amyloid Abeta aggregates and reagents to authenticate these preparations and specifically identify and quantify these polymorphs in vitro and in the brain. Such protocols and reagents are necessary to support basic research aimed at understanding the roles and mechanisms of amyloids in disease pathogenesis.

Therefore, the overall goal of this resource initiative is to establish a source network for the development of reagents and protocols for the production, standardization, characterization, authentication of amyloid oligomers and fibrils, and the dissemination of these materials to investigators.

Irvine University Of California

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

Irvine, California 926970001 United States

Single Zip Code

Resource Networks for Protein Polymorphisms in Alzheimers Disease and its Related Dementias (AD/ADRD) (U24 Clinical Trial Not Allowed) (RFA-AG-22-030)

Amendment Since initial award the total obligations have increased 258% from $1,265,234 to $4,533,350.