New York, May 30 : A team of researchers have identified a blood biomarker that can predict if a cognitively healthy person will go on to develop Alzheimer’s disease or not.
The team from the University of Pittsburgh found that star-shaped brain cells called astrocytes are the key to swaying the pendulum in Alzheimer’s disease progression.
They tested the blood of more than 1,000 cognitively unimpaired elderly people with and without amyloid pathology.
The results, published in the journal Nature Medicine, showed that only those who had a combination of amyloid burden and blood markers of abnormal astrocyte activation, or reactivity, would progress to symptomatic Alzheimer’s in the future, a critical discovery for drug development aimed at halting progression.
“Our study argues that testing for the presence of brain amyloid along with blood biomarkers of astrocyte reactivity is the optimal screening to identify patients who are most at risk for progressing to Alzheimer’s disease,” said Tharick Pascoal, Associate Professor of psychiatry and neurology at the varsity.
“This puts astrocytes at the centre as key regulators of disease progression, challenging the notion that amyloid is enough to trigger Alzheimer’s disease,” Pascoal added.
Scientists tested blood samples from participants in three independent studies of cognitively unimpaired elderly people for biomarkers of astrocyte reactivity — glial fibrillary acidic protein, or GFAP — along with the presence of pathological tau.
The study showed that only those who were positive for both amyloid and astrocyte reactivity showed evidence of progressively developing tau pathology, indicating predisposition to clinical symptoms of Alzheimer’s disease.
The findings have direct implications for future clinical trials for Alzheimer’s drug candidates.In aiming to halt disease progression sooner, trials are moving to earlier and earlier stages of pre-symptomatic disease, making correct early diagnosis of Alzheimer’s risk critical for success.
Because a significant percentage of amyloid-positive individuals will not progress to clinical forms of Alzheimer’s, amyloid positivity alone is not enough to determine an individual’s eligibility for a therapy.
Inclusion of astrocyte reactivity markers, such as GFAP, in the panel of diagnostic tests will allow for improved selection of patients who are likely to progress to later stages of Alzheimer’s and, therefore, help fine tune a selection of candidates for therapeutic interventions who are more likely to benefit, the researchers said.
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