番茄社区

A blood-based biomarker detected Alzheimer's disease with the same accuracy as more costly or invasive imaging or cerebrospinal fluid tests, researchers at the virtual Alzheimer's Association International Conference (AAIC) said.

In a study involving three selected cohorts, plasma tau phosphorylated at threonine 217 (p-tau217) discriminated Alzheimer's from other neurodegenerative diseases with significantly higher accuracy than established plasma and MRI biomarkers, reported Oskar Hansson, MD, PhD, of Skane University Hospital in Malmö, Sweden, and colleagues. The study was published simultaneously in .

And in data published in the , Nicolas Barthélemy, PhD, and Randall Bateman, MD, of Washington University School of Medicine in St. Louis, and colleagues, showed that while both p-tau217 and p-tau181 could predict the presence of amyloid plaques in PET scans, p-tau217 amyloid measures were superior.

In primary care practice, diagnostic work-ups of dementia disorders are not very accurate, Hansson noted. "We believe that plasma p-tau217 is likely to improve the diagnostic work-up of Alzheimer's disease during both the early stages of the disease as well as during the dementia phase," he said.

"Levels of p-tau217 increase only in Alzheimer's disease -- and not in other dementia disorders also characterized by tau pathology -- strongly indicating that plasma p-tau217 is very specific for Alzheimer's disease," Hansson told 番茄社区.

A p-tau217 blood test could be "a real game changer," noted Howard Fillit, MD, of the Alzheimer's Drug Discovery Foundation in New York City, who wasn't involved with either study.

"I really think this is going to be a huge advance in Alzheimer's disease. It's almost like the first steps that blood tests for cholesterol in heart disease took back in the 1950s and '60s," Fillit said in an interview with 番茄社区. "This might be the first of many blood tests for tau that may come out, but this one is good enough."

In the JAMA study, Hansson and colleagues looked at three cross-sectional cohorts:

• A neuropathology cohort of 34 participants with Alzheimer's and 47 without
• A Swedish BioFINDER-2 cohort of 301 cognitively unimpaired participants, 178 people clinically diagnosed with mild cognitive impairment (MCI), 121 people with Alzheimer's dementia, and 99 people with other neurodegenerative diseases such as progressive supranuclear palsy, vascular dementia, and frontotemporal dementia
• A cohort of people with genetically-caused Alzheimer's (Colombian autosomal-dominant Alzheimer's registry), including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers

In the pathology cohort, plasma p-tau217 differentiated neuropathologically-defined Alzheimer's disease from non-Alzheimer's (AUC 0.89) with significantly higher accuracy than plasma p-tau181 and neurofilament light chain (AUC range, 0.50-0.72, P<0.05). Plasma p-tau217 levels correlated with tau tangles in participants with but not without amyloid beta (Aβ) plaques.

In the Swedish BioFINDER study, the discriminative accuracy of plasma p-tau217 for clinical Alzheimer's dementia versus other neurodegenerative diseases (AUC 0.96) was significantly higher than plasma p-tau181, plasma neurofilament light, and MRI measures (AUC range, 0.50-0.81, P<0.001) but not significantly different than CSF p-tau217, CSF p-tau181, and tau-PET (AUC range, 0.90-0.99, P>0.15). Plasma p-tau217 discriminated abnormal from normal tau PET scans (AUC 0.93) with significantly higher accuracy than plasma p-tau181, plasma neurofilament light, CSF p-tau181, CSF Aβ42:Aβ40 ratio, and MRI measures (AUC range 0.67-0.90, P<0.05), and was similar to CSF p-tau217 (AUC 0.96, P=0.22).

In the Colombian autosomal-dominant group, plasma p-tau217 was significantly greater in PSEN1 mutation carriers about 20 years before estimated onset of MCI. Plasma p-tau217 levels increased by age in PSEN1 E280A mutation carriers, with significant differences from noncarriers emerging at age 25.

In the other paper, Barthélemy, Bateman, and colleagues extended their previous work with p-tau217, using mass spectrometry to identify whether plasma p-tau isoforms could detect Alzheimer's pathology. In a discovery cohort of 36 people, p-tau217 and p-tau181 were highly specific for amyloid plaque pathology (AUC 0.99 and 0.98, respectively). In a validation cohort of 92 people, p-tau217 still was specific to amyloid status (AUC 0.92), but p-tau181 measures were less specific (AUC 0.75).

To develop and validate Alzheimer's blood biomarkers, Washington University researchers have launched the study, which will enroll more than 1,100 people in greater St. Louis with diversity in race, socioeconomic status, medical history, and cognitive status -- "average people, not 'super volunteers' in Alzheimer's disease studies," Bateman noted in a press conference. "These people will tell us a lot more about how these tests will perform in the clinic," he said.

A blood test also could open up the research community to "all kinds of studies that were unimaginable before," he pointed out. "That's going to revolutionize how fast we move toward effective treatments and prevention in Alzheimer's disease."