R01AG070941

Staging Alzheimer's Disease with Blood-Based Biomarkers

The brain changes associated with Alzheimer's Disease (AD) begin many years before the onset of cognitive symptoms. Most models of AD propose a stepwise progression of brain pathology, starting with the deposition of amyloid plaques, followed by tau tangle formation, and ultimately leading to neurodegeneration. While cerebrospinal fluid (CSF) and imaging biomarkers have been developed to detect AD brain pathology in living individuals, these modalities have significant drawbacks that limit their widespread use.

In recent years, there has been rapid development of blood-based biomarkers that accurately detect AD brain pathology. In this study, we aim to investigate some of the most promising blood-based biomarkers for three types of AD brain pathology: amyloid (ASS42/ASS40), tau (phosphorylated tau [PTAU] isoforms), and neurodegeneration (neurofilament light chain protein [NFL]).

Our research team has developed immunoprecipitation-mass spectrometry assays for plasma ASS42/ASS40 and PTAU isoforms, which will be further optimized and automated as part of the proposed project. We will be studying the Knight Alzheimer Disease Research Center cohort, which has available data on plasma and CSF NFL, clinical dementia diagnosis, performance on cognitive tests, health history, amyloid PET, tau PET, structural brain volumes by MRI, genetic markers, numerous CSF biomarker measures, discovery proteomics data, and autopsy reports.

Approximately 1,700 matched pairs of banked plasma and CSF samples from around 1,000 individuals will be examined, a size similar to recent major studies of cognitive outcomes in relation to biomarker combinations. We will evaluate the correlation of the blood-based measures with well-established CSF and imaging measures. Biomarkers of amyloid, tau, and neurodegeneration will be used independently and in combination within a modality (blood-based, CSF, or imaging) to predict the risk for current or future symptomatic AD.

For all analyses, we will also evaluate the effects of individual characteristics, including age, sex, years of education, APOE E4 genotype, polygenic risk score, race, and medical comorbidities, to identify factors that modify the expression of symptoms associated with biomarker levels. Our hypothesis is that the combination of plasma ASS42/ASS40, PTAU isoforms, and NFL will outperform amyloid PET in predicting the risk for current or future symptomatic AD.

Given that blood tests are well-accepted by patients, physicians, and researchers, an accurate blood test for symptomatic AD would likely be widely used and could be a game-changer in improving AD research, accelerating clinical trials, and enabling more accurate diagnoses in the clinic.

Washington University

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]

Saint Louis, Missouri 63130 United States

Single Zip Code

Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional) (PAR-19-070)

Amendment Since initial award the total obligations have increased 218% from $1,360,491 to $4,319,929.