Research Offers New Hope for Predicting Alzheimer’s Progression

By Cari Wade Gervin
Tuesday, March 30, 2021

Three new studies show protein biomarkers can identify Alzheimer’s Disease years before people have symptoms.

While a cure for Alzheimer’s disease remains far away, new research shows promise in detecting who will develop the condition years before symptoms begin.

“There’s a 10-year symptomatic period for Alzheimer’s, but two-thirds of the course of the disease is happening before the person knows it ... [It is] only the last third of the disease that the person is dealing with symptoms,” says Randall J. Bateman, MD, Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington University School of Medicine in St. Louis. “Without symptoms, we have really no other way to stage people, except the biomarkers.”

Dr. Bateman and his research team published a study in the journal Brain documenting a novel protein — microtubule binding region tau (MTBR tau) — in the cerebrospinal fluid. This biomarker shows the level of tau tangles in the brain, indicating the progress of the disease.

“We think this is going to be useful in the future because we’ll be able to utilize this in trials where we’re testing new tau treatments,” Dr. Bateman says. “We’ll also be able to utilize it potentially one day as a biomarker to help diagnose Alzheimer’s disease.”

Other Studies Show Similar Results

A second study published in Alzheimer’s & Dementia recently shows that different p-tau biomarkers change at distinct stages as Alzheimer’s disease progresses, which could also lead to targeting specific p-tau therapeutically at different stages of the disease.

“A possible way to improve the chances of future therapies is to test them on people in the very early stages of the disease with elusive biological changes but lacking clinical symptoms, including memory failings,” says Kaj Blennow, professor of neurochemistry at the University of Gothenburg in Gothenburg, Sweden, who directed the research. “The practical challenge, however, is that these very tiny initial changes are incredibly difficult to measure reliably.”

Another recent study in Alzheimer’s Research & Therapy offers hope for a diagnostic blood test prior to symptoms developing. Using an immuno-infrared sensor, researchers looked at levels of misfolding of the amyloid-beta (Aβ) peptide, another biomarker for Alzheimer’s disease, in blood plasma. At the time of the first test, none of the 203 subjects showed any cognitive decline via the usual diagnostic tests. However, within six years, all 22 patients who had Aβ misfolding had developed Alzheimer’s disease, and those with severe misfolding developed the condition sooner.

Although the study was small, it suggests biomarker monitoring could soon become the gold standard for Alzheimer’s disease diagnosis and staging, as therapies applied in the nonclinical stage may be able to improve outcomes and enhance therapy response.