Who is Most Likely to Benefit From Therapies Curbing Early Alzheimer’s? A Blood Test Can Provide Clues, Pitt Research Says

By: Anastasia Gorelova

A simple blood test can help identify individuals most at risk of developing neurological symptoms of Alzheimer’s disease, according to new research led by University of Pittsburgh School of Medicine scientists.

“By using blood measures that define signs of amyloid pathology and neurodegeneration we can identify who is going to decline fastest and should be prioritized for intervention,” said Dr. Thomas Karikari, assistant professor of psychiatry at the University of Pittsburgh.

Dr. Thomas Karikari

The study, published recently in the journal Nature Communications, builds on Karikari’s earlier work with his former colleagues at the University of Gothenburg, Sweden. Their previous research, published a little over a year ago, showed that this new blood testing method could selectively detect a protein called brain-derived tau, or BD-tau, and identify signs of Alzheimer’s-associated neurodegeneration.

The latest research showed that including BD-tau in a diagnostic panel of blood biomarkers can help identify which individuals are most at risk for Alzheimer’s-associated dementias and memory loss, giving doctors the opportunity to effectively tailor therapies to each patient’s prognosis.

To diagnose Alzheimer’s disease, neurologists rely on a panel of blood-, spinal fluid- or brain-imaging-based biomarkers in addition to performing neurological examinations. Detecting amyloid plaques and the phosphorylated form of tau tangles – abnormal proteins that accumulate in the brain – has, in recent years, become a reliable way to identify two out of the three components of Alzheimer’s pathology.

The third component – markers of Alzheimer’s neurodegeneration – has proven more challenging to detect. Many proposed markers of neurodegeneration can be imprecise: For example, blood levels of neurofilament light, an indicator of nerve cell damage, become elevated in Alzheimer’s disease, Parkinson’s and other dementias, rendering it less useful when trying to differentiate Alzheimer’s disease from other neurodegenerative conditions.

In the new study, which included healthy participants as well as patients admitted to memory clinics in Norway, Sweden and Spain, Karikari and his team found that people whose blood samples were positive for phospho-tau and BD-tau and had high levels of amyloid in their brains had the fastest cognitive decline compared to patients who had signs of amyloid pathology but no detectable BD-tau presence.

In addition, unlike neurofilament light, levels of which naturally increase in blood with age, BD-tau levels were not associated either with age or race, and not affected by poor kidney function or diabetes, making it a more reliable option for screening patients across a wide health spectrum.

With the new arrival of anti-amyloid therapies, that knowledge is critical. In order for the newly FDA-approved drugs to succeed, they must be given early in Alzheimer’s progression, making it increasingly more important to easily and quickly identify patients who may not yet be noticeably symptomatic.

“Clinicians are looking for ways to ethically select patients who are most likely to benefit from therapies that are still scarce and tightly regulated,” Karikari said. “Right now, we are focused on integrating these biomarkers into the clinic and understanding how they can affect clinical decision making.”