Tests for Alzheimer’s disease show promise

In converging studies, four teams of scientists say they are getting closer to developing blood tests that could detect Alzheimer’s disease before cognitive decline sets in.

Currently, early detection of the most common form of dementia is achieved using positron emission tomography (PET) brain scans or a spinal tap to test cerebrospinal fluid.

They detect abnormal levels of the beta-amyloid protein, which forms plaques, and another protein called tau that creates neurofibrillary tangles – both of which, among other factors, cause brain degeneration.

But these gold standard measures are costly and invasive.

“There is an urgent need for simple, inexpensive tests, non-invasive and easily availably diagnostic tools for Alzheimer’s,” says Maria Carrillo, chief science officer at the Alzheimer’s Association in Chicago, US, which is hosting an international virtual conference.

“The possibility of early detection and being able to intervene with a treatment before significant damage to the brain from Alzheimer’s disease would be game changing for individuals, families and our healthcare system.”

All four new studies focus on developing tests to detect a form of tau known as p-tau-217 in blood plasma and are reporting encouraging findings.

Oskar Hansson from Sweden’s Lund University and colleagues presented results of a blood test they say is as accurate at detecting this biomarker as PET scans and spinal fluid. Their findings also are published in the journal JAMA.

The team validated its blood test in more than 1400 people with, or at risk for, dementia from three different cohorts, confirming it could reliably distinguish Alzheimer’s disease from other neurodegenerative disorders with between 89% and 98% accuracy.

They also found that levels of p-tau-217 were around seven times higher in people with Alzheimer’s and detected increased levels 20 years before signs of cognitive impairment in people with a gene that causes the disease.

“This test, once verified and confirmed, opens the possibility of early diagnosis of Alzheimer’s before the dementia stage,” says Hansson.

Another group, led by Suzanne Schindler from Washington University, US, reported to the conference that blood plasma levels of p-tau-17 are closely linked to amyloid plaques in the brain as measured by a PET scan.

They are evaluating several different amyloid and tau indicators, which they say could enable earlier and more accurate dementia diagnosis and track the stages of Alzheimer’s progression. They’ve now launched a large trial to test and validate the blood biomarkers.

A third team – from the UCSF Memory and Aging Centre, US, led by Elisabeth Thijssen and Adam Boxer – has compared p-tau-217 with another protein previously proposed as a biomarker for Alzheimer’s called p-tau-181 in more than 600 people.

It told the conference that p-tau-181 is more than three times higher in people with Alzheimer’s compared to healthy adults or those with a neurodegenerative disease called frontotemporal lobar degeneration (FTLD).

But plasma levels of p-tau-217 were even higher, with a five-fold increase compared to FTLD and healthy controls. Both proteins corresponded closely with PET scan results.

These findings concur with a separate study from Washington University, just published in the Journal of Experimental Medicine.

Led by Nicolas Barthélemy and Randall J Bateman, it found that, as in cerebrospinal fluid, blood plasma levels of p-tau-217 are extremely low in healthy volunteers and high in people with amyloid plaques before symptoms of cognitive decline appear.

Their mass spectometry tests of p-tau-217 were more accurate than p-tau-181 at predicting the presence of amyloid plaques in PET scans.

“Our findings support the idea that tau isoforms in the blood are potentially useful for detecting and diagnosing Alzheimer’s disease pathology,” says Bateman.

Two Australian experts not associated with the research agree that both the studies already published show promise.

“These two independent papers provide compelling evidence that it is possible to use blood plasma assays of p-tau to diagnose Alzheimer’s disease specifically and with a high degree of accuracy,” says Colin Masters from the University of Melbourne.

He notes that both methods seem to work long before symptoms appear in early-onset Alzheimer’s, but says it remains to be seen if they can detect the more common late-onset disease.

“A blood test that could diagnose Alzheimer’s disease early is highly desirable,” says Ian Musgrave from the University of Adelaide, agreeing that both studies take us closer to achieving that.

“Both show a good association with Alzheimer’s disease and the ability to discriminate between Alzheimer’s and other forms of neurodegeneration,” he says.

“Importantly, these tests may be able to pick up Alzheimer’s before significant damage has occurred. However, there is still a way to go.”

He notes that they need to be trialled in larger populations with more diverse clinical conditions and that the specialised tests won’t be easily accessible for some time yet.