New Blood Test May Provide Early Detection of Alzheimer’s Disease

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Tau protein in Alzheimer's disease, illustration
Pathological phosphorylation (yellow) of Tau proteins (orange) by kinases (blue-purple) affect nerve cells in what is called a neurofibrillary tangle.

A new blood-based test for Alzheimer’s Disease (AD) has shown promising results distinguishing between people with and without the disease and may even be able to detect it as early as 20 years before the onset of cognitive symptoms. The research, by an international team of investigators included 1,402 participants, both impaired and unimpaired from from studies in Arizona, Sweden, and Colombia.

The findings, “Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders” were published in the Journal of the American Medical Association (JAMA) and presented at the Alzheimer’s Association International Conference.

For many years, the diagnosis of Alzheimer’s has been based on the characterization of amyloid plaques and tau tangles in the brain, typically after a person dies. According to the new study, measurements of phospho-tau217 (p-tau217), one of the tau proteins found in tangles, could provide a sensitive and accurate indicator of plaques and tangles—corresponding to the diagnosis of Alzheimer’s—in living people.

It is estimated that approximately 100 million people worldwide will have AD dementia in 2050. The researchers sought to determine the diagnostic accuracy of plasma P-tau217 for Alzheimer’s in both for distinguishing clinically diagnosed AD dementia from other neurodegenerative diseases and neuropathologically defined AD from non-AD individuals. The accuracy of plasma P-tau217 was compared with other key plasma, CSF, PET, and magnetic resonance imaging (MRI) biomarkers for AD.

“The p-tau217 blood test has great promise in the diagnosis, early detection, and study of Alzheimer’s,” said Oskar Hansson, M.D., Ph.D., professor of clinical memory research at Lund University, Sweden, who leads the Swedish BioFINDER Study and senior author on the study, spearheading the international collaborative effort.

More work is needed to optimize the assay and more testing is needed before it becomes available in the clinic. Hansson believes the blood test may be able to improve the recognition, diagnosis, and care of people in the primary setting.

The research included 81 Arizona participants in Banner Sun Health Research Institute’s Brain Donation program, who had clinical assessments and provided blood samples in their last years of life and then had neuropathological assessments after they died; 699 participants in the Swedish BioFINDER Study who had clinical, brain imaging, cerebrospinal fluid (CSF), and blood-based biomarker assessments; and 522 Colombian autosomal dominant Alzheimer’s disease (ADAD)-causing mutation carriers and non-carriers from the world’s largest ADAD cohort.

In the Arizona cohort, the plasma p-tau217 assay distinguished between Arizona Brain donors with and without the subsequent neuropathological diagnosis of “intermediate or high likelihood Alzheimer’s” (i.e., characterized by plaques, as well as tangles that have at least spread to temporal lobe memory areas or beyond) with 89% accuracy; it distinguished between those with and without a diagnosis of “high likelihood Alzheimer’s” with 98% accuracy; and higher ptau217 measurements were correlated with higher brain tangle counts only in those persons who also had amyloid plaques.

In the Swedish study, the assay distinguished between persons with the clinical diagnoses of Alzheimer’s and other neurodegenerative diseases with 96% accuracy, similar to tau PET scans and CSF biomarkers and better than several other blood tests and MRI measurements; and it distinguished between those with and without an abnormal tau PET scan with 93% accuracy.

The assay in the Columbia cohort began to distinguish between mutation carriers and non-carriers 20 years before their estimated age at the onset of mild cognitive impairment.

The researchers noted, “The neuropathology cohort (cohort 1) with antemortem plasma samples included 81 participants. Eighteen (22%) had intermediate likelihood and 16 (20%) had high likelihood of AD. These 34 (42%) comprised the AD group; of these, 27 had dementia. Forty-seven (58%) comprised the non-AD group. The BioFINDER-2 study (cohort 2) included 699 clinically diagnosed participants, of whom 301 (43%) were controls (i.e., cognitively unimpaired), 178 (25%) had MCI, 121 (17%) had AD with dementia, and 99 (14%) had various other neurodegenerative diseases. The Colombian autosomal-dominant AD registry (cohort 3) included 622 participants, of whom 365 (59%) were PSEN1 mutation carriers and 257 (41%) age- and sex-matched noncarriers (controls). Among the mutation carriers, 259 (71%) were cognitively unimpaired and 106 (29%) cognitively impaired.”

Researchers have made great progress in previous years in the development of amyloid blood tests. While more work is still needed before clinical use, the new blood test holds promise to advance the disease’s research and care in other important ways.

Eric Reiman, M.D., executive director of Banner Alzheimer’s Institute in Phoenix and a senior author on the study, added: “Blood tests like p-tau217 have the potential to revolutionize Alzheimer’s research, treatment, and prevention trials, and clinical care.”

“While there’s more work to do, I anticipate that their impact in both the research and clinical setting will become readily apparent within the next two years,” Reiman concluded.

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