In one new development, experts at the University of California, San Francisco (UCSF) compared phosphorylated-tau181 (P-tau181) to a related form of tau called P-tau217 to determine which can best identify individuals with Alzheimer’s disease.
Results showed that the two biomarkers were similar overall, but P-tau 217 had a slight edge in terms of accuracy. Importantly, both tau isoforms distinguished frontotemporal lobar degeneration (FTLD).
“These new blood tests for P-tau are going to be really exciting because they will improve our ability to simply and inexpensively assess whether someone is at high risk for having Alzheimer’s disease,” said study author, professor in UCSF’s department of neurology.
With the approval of the first disease-modifying therapy for Alzheimer’s disease possibly around the corner, developing an accurate diagnostic blood test for this condition is even more urgent, added Dr. Boxer, who is also director of UCSF’s Neurosciences Clinical Research Unit and AD and FTD Clinical Trials Program.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference.
Currently, the only approved Alzheimer’s disease biomarkers are expensive positron emission tomography (PET) scans using agents that detect tau or amyloid, another hallmark Alzheimer’s disease protein, and cerebrospinal fluid levels of amyloid and tau, the measurement of which entails invasive lumbar puncture procedures. This limits the ability to easily confirm the underlying cause of dementia or cognitive impairment, which “obviously has important prognostic and therapeutic implications,” said Dr. Boxer.
Having a plasma biomarker, especially for tau, would be extremely useful. Patients with increased tau in the brain tend to exhibit Alzheimer’s disease symptoms while those with amyloid plaques do not always have clear signs, at least not immediately. “We think that P-tau is probably a better measure because it is much more closely related to symptoms of disease,” said Dr. Boxer.
Earlier this year, he and colleagues published a study in Nature Medicine showing that P-tau181 is more than three times as high in individuals with Alzheimer’s disease compared with healthy elderly people. It also differentiated Alzheimer’s disease from frontotemporal dementia (FTD). “We found that P-tau 181 was almost as good as a PET scan or lumbar puncture at identifying individuals with Alzheimer’s disease pathology in the brain,” said Dr. Boxer.
They next wanted to assess how well P-tau 217 held up as a possible biomarker.
The new retrospective study was composed of 210 participants: 37 who acted as healthy controls, 99 who had FTLD, 39 who had Alzheimer’s disease, and 35 who had mild cognitive impairment.
More accurate test
Results showed that plasma P-tau217 was increased 5.7-fold in the participants with Alzheimer’s disease compared with the healthy controls group, and increased fivefold compared with those who had FTLD (both comparisons, P < .001).
The increase in plasma P-tau181 was lower. It was increased only 4.5-times in participants with Alzheimer’s disease compared with the healthy controls and 3.8-times relative to those with FTLD (both, P < .001). In addition, P-tau217 was potentially superior in predicting whether a person had a tau positive FTP-PET brain scan.
“This newer P-tau 217 test produces very similar results to the previous test we published [on P-tau181], but might be incrementally better or slightly more accurate, and even more closely related to the signal you get with a tau PET scan,” Dr. Boxer said.
The researchers are now examining these issues in a larger group of participants (N = 617). Results for those analyses are expected to be published soon. In addition to tau and amyloid markers, the researchers are examining another potential biomarker of neurodegeneration: the triple protein neurofilament light chain.
It’s too early to say which biomarker or biomarkers will prove to be the most useful in diagnosing Alzheimer’s disease, Dr. Boxer noted. “It’s an open question whether it will be necessary to measure multiple P-taus plus beta amyloid plus neurofilament, or maybe just measuring one P-tau level will be sufficient,” he said.