P-tau217 Differentiates AD vs Other Neurodegenerative Conditions

Megan Brooks

July 29, 2020

A blood test that measures plasma tau phosphorylated at threonine 217 (P-tau217) can accurately distinguish Alzheimer's disease (AD) from other neurodegenerative disorders, new research suggests.

Results from a large multinational study showed that the level of P-tau217 in blood collected during life was an accurate predictor of tau brain changes seen in brain tissue after death.

In addition, increasing blood P-tau217 levels can be detected in some individuals up to 20 years before the average age of onset of the early cognitive decline that signals AD, researchers report.

"While there is still more work to be done, this biomarker has the potential to have a transformational impact on research, treatment, prevention, and therapy development, and in the clinical setting," senior author Eric Reiman, MD, executive director of Banner Alzheimer's Institute in Phoenix, Arizona, told Medscape Medical News.

The findings were presented at the Alzheimer's Association International Conference (AAIC) 2020, which was held online this year because of the COVID-19 pandemic, and simultaneously published online July 28 in JAMA.

Three Cohorts

The international team of researchers evaluated the P-tau217 blood test in 1402 adults from three cohorts.

The first cohort was comprised of 81 individuals in the Arizona (Banner Sun Health Research Institute) Brain Donation program and included clinical, blood, and neuropathological data.

The second cohort included 699 individuals in the Swedish BioFINDER-2 study and provided clinical, brain imaging, CSF, and blood data.

The third cohort was made up of 522 participants from the Columbian autosomal-dominant AD kindred, including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers.

In the Arizona cohort, plasma P-tau217 discriminated neuropathologically defined AD from non-AD (AUC, 0.89; 95% CI, 0.81 - 0.97) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P < .05).

In the Swedish BioFINDER-2 cohort, the discriminative accuracy of plasma P-tau217 for clinical AD dementia versus other neurodegenerative diseases was 96% (AUC, 0.96; 95% CI, 0.93 - 0.98).

This was significantly higher than plasma P-tau181, plasma NfL, and MRI measures (AUC range, 0.50-0.81; P < .001), but was not significantly different than CSF P-tau217, CSF P-tau181, and tau-PET (AUC range, 0.90-0.99; P > .15).

In the Colombian cohort, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers than noncarriers starting at around age 25 years, which is 20 years prior to the estimated onset of mild cognitive impairment among mutation carriers.

Additionally, plasma P-tau217 levels correlated with cerebral tau tangles, and discriminated abnormal versus normal tau-PET scans with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Aβ42:Aβ40 ratio, and MRI measures.

The blood test "opens the possibility of early diagnosis of Alzheimer's before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process," presenting author Oskar Hansson, MD, PhD, Lund University, Sweden, said in a statement.

Further research is now needed to optimize the P-tau217 blood test, validate the findings in unselected and diverse populations, and determine its potential role in the clinic, the investigators note.

Game Changer?

Commenting on the study for Medscape Medical News, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer's Drug Discovery Foundation, noted his enthusiasm for the test.

"This tau blood test will be a real game changer, advancing clinical care and research," said Fillit, who was not involved in the research.

"This is a real breakthrough: a simple and accessible blood test that can diagnose Alzheimer's better than the more costly and invasive methods currently available like PET scans and cerebrospinal fluid biomarkers," he said.

The P-tau217 blood test "is like the equivalent of the cholesterol test for heart disease, but for Alzheimer's disease," Fillit added.

As reported by Medscape Medical News, another study presented at AAIC 2020 compared P-tau217 with P-tau181 to determine which could best identify individuals with AD.

Results showed that although the two biomarkers were similar overall, P-tau217 had a slight edge in terms of accuracy.

The study was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Alzheimer Foundation. Hansson has reported receiving grants from Roche, Biogen, and Pfizer, and receiving nonfinancial support from GE Healthcare, AVID Radiopharmaceuticals, and Euroimmun. Reiman has received grants from Roche/Roche Diagnostics and received personal fees from Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, MagQ, Takeda/Zinfandel, and United Neuroscience. He is also a cofounder of AlzPath, which aims to further develop P-tau217 and fluid biomarkers; holds a patent owned by Banner Health for a strategy to use biomarkers to accelerate evaluation of Alzheimer prevention therapies; and is a principal investigator of prevention trials that include research agreements with Genentech/Roche and Novartis/Amgen, PET studies that include research agreements with Avid/Lilly, and several National Institue of Health and Foundation-supported research studies. Fillit has reported no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2020. Presented July 28, 2020.

JAMA. Published July 28, 2020. Full text

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