Progress in Research for Alzheimer's Test

Researchers report an advance in the development of a blood test that could help detect Alzheimer’s disease in people who are showing signs of dementia. This approach could be less invasive and less costly than current brain imaging and spinal fluid tests. The blood test detects the abnormal accumulation of a form of tau protein known as phosphorylated-tau-181 (ptau181), which is a biomarker that suggests brain changes from Alzheimer’s. The study, funded by the National Institutes of Health (NIH), was published in Nature Medicine.

Over the past 15 years, research advances in the development of biomarkers like tau protein have enabled investigators to more accurately diagnose Alzheimer’s disease, select research participants, and measure response to investigational therapies. Tau and other biomarkers can be detected with PET scans of the brain and lab tests of spinal fluid. However, PET imaging is expensive and involves radioactive agents, and spinal fluid tests require spinal taps, which are invasive, complex and time-consuming. Simpler biomarker tests are still needed.

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“The considerable time and resources required for screening research participants with PET scans and spinal taps slow the pace of enrollment for Alzheimer’s disease treatment studies,” said Richard J. Hodes, M.D., director of NIH’s National Institute on Aging (NIA), which funded much of the study. “The development of a blood test would enable us to rapidly screen a much larger and more diverse group of volunteers who wish to enroll in studies.”

An international team of researchers led by Adam Boxer, M.D., Ph.D., at the University of California, San Francisco, used the new test to measure the concentration of ptau181 in plasma, which is the liquid part of blood that carries the blood cells. The samples were collected from more than 400 participants from the University of California, San Francisco Memory and Aging Center, part of the NIA-funded Alzheimer’s Disease Research Center; the NIH-supported Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) consortium; and a research study sponsored by Eli Lilly.

The investigators’ analysis demonstrated that the ptau181 in plasma could differentiate healthy participants from those with Alzheimer’s pathology, and differentiate those with Alzheimer’s pathology from a group of rare neurodegenerative diseases known collectively as frontotemporal lobar degeneration (FTLD).

“It has become clear that there are many possible biological pathways to dementia,” said Roderick Corriveau, Ph.D., program director at NIH’s National Institute of Neurological Disorders and Stroke (NINDS), which also supported the study. “Finding a blood test that specifically identifies the presence of Alzheimer’s pathology in the brain should greatly help researchers develop better treatments for the many who suffer from dementia.”

In addition, the results with the plasma ptau181 test mirrored results with two established biomarker tests for Alzheimer’s — a spinal fluid ptau181 test and a PET brain scan biomarker known as amyloid protein. The research team, which includes the NIH’s ARTFL–LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) research consortium that was announced last year, is now aiming to refine and improve the ptau181 blood test method

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