New blood test can track Alzheimer’s progression

By Stephen Beech

A new "highly accurate" blood test for Alzheimer’s disease also measures how far it has progressed.

It could help enable personalized treatment for dementia patients, say scientists.

Several blood tests for Alzheimer’s are already clinically available, including two based on technology licensed from Washington University School of Medicine in St. Louis, Mo.

The tests help doctors diagnose the neurodegenerative condition in people with symptoms but don't indicate the degree of impairment in thinking or memory due to Alzheimer’s dementia.

Current Alzheimer’s therapies are most effective in early stages of the disease.

Having a relatively easy and reliable way to gauge how far the disease has progressed could help doctors determine which patients are likely to benefit from drug treatment and to what extent, say scientists.

The new test, developed by researchers at Washington University School of Medicine and Lund University in Sweden, can also provide insight on whether a person’s symptoms are likely due to Alzheimer’s or some other cause.

The study, published in the journal Nature Medicine, shows that levels of a protein called MTBR-tau243 in the blood accurately reflect the amount of toxic accumulation of tau aggregates in the brain and correlate with the severity of Alzheimer’s disease.

By analyzing blood levels of MTBR-tau243 in a group of people with cognitive decline, the research team were able to distinguish between people with early- or later-stage Alzheimer’s disease and separate both groups of Alzheimer’s patients from people whose symptoms were caused by something else.

Study co-senior author Dr. Randall Bateman, of Washington University School of Medicine, said: “This blood test clearly identifies Alzheimer’s tau tangles, which is our best biomarker measure of Alzheimer’s symptoms and dementia.

“In clinical practice right now, we don’t have easy or accessible measures of Alzheimer’s tangles and dementia, and so a tangle blood test like this can provide a much better indication if the symptoms are due to Alzheimer’s and may also help doctors decide which treatments are best for their patients.”

He explained that Alzheimer’s involves a build-up of a protein, called amyloid, into plaques in the brain, followed by the development of tangles of tau protein years later.

Cognitive symptoms start to show at around the time tau tangles become detectable, and symptoms worsen as the tangles spread.

The "gold standard" for staging Alzheimer’s disease is positron emission tomography (PET) brain scans for amyloid plaques and tau tangles.

Amyloid scans yield information about the pre-symptomatic and early symptomatic stages, while tau scans are useful for tracking later stages of the disease.

The researchers say PET brain scans are highly accurate but expensive, time-consuming and frequently unavailable outside of major research centers, so they are not widely used.

Dr. Bateman leads a team that is developing blood tests for Alzheimer’s disease as a more accessible alternative to brain scans.

The team has developed two blood tests that correlate closely with the amount of amyloid plaques in the brain. Both are now used by doctors to aid diagnosis.

But, until now, there has been no blood test that reports on tau levels in the brain.

The researchers found that blood MTBR-tau243 levels reflected the amount of tau tangles in the brain with 92% accuracy.

MTBR-tau243 levels in the blood were normal in asymptomatic people regardless of amyloid status, meaning that blood MTBR-tau243 levels do not change between healthy people and people in the pre-symptomatic stage of Alzheimer’s disease with amyloid plaques.

Among people with cognitive symptoms due to Alzheimer’s disease, MTBR-tau243 levels were "significantly elevated" for people in the mild cognitive impairment phase of Alzheimer’s and up to 200 times higher for those in the dementia phase.

Those differences translated into "clear separation" of people in early- and late-stage Alzheimer’s disease, according to the researchers.

At the same time, MTBR-tau243 levels were normal in people with cognitive symptoms due to diseases other than Alzheimer’s, meaning that the test effectively distinguished Alzheimer’s dementia from other kinds of dementia.

The technology underlying the blood test for tau aggregates has been licensed by Washington University to C2N Diagnostics, a start-up that developed the blood tests for amyloid. The amyloid tests incorporate measures of another form of tau called p-tau217.

Study co-senior author Dr. Oskar Hansson, a neurologist at Lund University, said: “I believe we will use blood-based p-tau217 to determine whether an individual has Alzheimer’s disease, but MTBR-tau243 will be a highly valuable complement in both clinical settings and research trials.

“When both of these biomarkers are positive, the likelihood that Alzheimer’s is the underlying cause of a person’s cognitive symptoms increases significantly, compared to when only p-tau217 is abnormal.

"This distinction is crucial for selecting the most appropriate treatment for each patient.”

Two Alzheimer’s therapies have been approved by the Food and Drug Administration (FDA) to slow progression of the disease, and both work by lowering amyloid levels in the brain.

Co-first author Dr. Kanta Horie said the number and variety of available Alzheimer’s medications may soon be expanding, as several experimental drugs that target tau or other aspects of Alzheimer’s disease are in the pipeline.

He says that with blood tests to diagnose and work out the stage the disease, doctors would be able to tailor treatments to a patient’s particular needs.

Dr. Horie, also of Washington University Medicine, added: “We’re about to enter the era of personalized medicine for Alzheimer’s disease.

“For early stages with low tau tangles, anti-amyloid therapies could be more efficacious than in late stages.

"But after the onset of dementia with high tau tangles, anti-tau therapy or one of the many other experimental approaches may be more effective.

"Once we have a clinically available blood test for staging, plus treatments that work at different stages of the disease, doctors will be able to optimize their treatment plans for the specific needs of each patient.”