New blood biomarker makes it possible to anticipate whether an elderly person will develop Alzheimer’s

Why do some people suffer? Alzheimer’s and others not? And why do many individuals with the brain packed with toxic amyloid aggregates – a biomarker of Alzheimer’s disease- never develop dementia associated with this pathology?.

Scientists at the University of Pittsburgh School of Medicine believe they have found the answer: Star-shaped brain cells called astrocytes hold the key to tipping the scales in Alzheimer’s disease to one side or the other.

The researchers have reached this conclusion after carrying out a study whose results have been published this Monday in “Nature Medicine”‘.

By analyzing the blood of more than a thousand elderly people without cognitive impairment, with and without amyloid pathology, the team found that only those with a combination of amyloid load and blood markers of abnormal astrocyte activation would suffer from Alzheimer’s disease, a critical discovery. to develop drugs to stop the progression.

“Our study argues that analysis for the presence of cerebral amyloid in conjunction with blood biomarkers of astrocyte reactivity is the optimal screening method to identify patients at increased risk of progressing to Alzheimer’s disease.”summarizes Tharick Pascoal, Associate Professor of Psychiatry and Neurology at Pitt.

“That is, astrocytes are key regulators of disease progression. Amyloid alone is not enough to trigger Alzheimer’s disease.”underline.

Alzheimer disease

Alzheimer’s is a neurodegenerative disorder that causes progressive memory loss and dementia, significantly reducing quality of life.

This disease is characterized by the accumulation of amyloid plaques (protein aggregates that lodge between nerve cells in the brain) and disordered groups of protein fibers, called tau tangles, that form inside neurons.

For decades, neuroscientists have believed that the buildup of amyloid plaques and tau tangles is not only a sign of Alzheimer’s disease, but also its cause, which is why existing drugs have targeted amyloid and tau and ignored others. brain processes.

But recent findings from groups like Pascoal’s suggest that some alterations in the brain, such as increased brain inflammation, could be just as important as amyloid load.

Two years ago, Pascoal discovered that inflammation of brain tissue triggers the spread of pathologically misfolded proteins in the brain and is a direct cause of eventual cognitive decline in patients with Alzheimer’s disease.

Now this team has discovered that cognitive decline can be predicted by a blood test.

Astrocytes are cells in brain tissue that supply neurons with oxygen and nourishment and protect them from pathogens, but because they do not conduct electricity and did not appear to play a direct role in communication between neurons, their role in disease had been overlooked. . Pitt’s latest research changes this situation.

The team analyzed blood samples from participants in three independent studies of the elderly without cognitive impairment for biomarkers of astrocyte reactivity — glial fibrillary acidic protein, or GFAP — along with the presence of pathologic tau.

The study demonstrated that only those who tested positive for both amyloid and astrocyte reactivity showed evidence of progressive development of tau pathology, indicating a predisposition to clinical symptoms of Alzheimer’s disease.

The results have direct implications for future clinical trials of Alzheimer’s drug candidates.

Since a significant percentage of amyloid-positive individuals do not develop Alzheimer’s, amyloid positivity alone is not sufficient to determine whether or not an individual should receive therapy. For this, it is necessary to add markers of astrocyte reactivity, such as GFAP, the study points out.

The inclusion of other markers in diagnostic tests will improve the selection of patients likely to progress to later stages of Alzheimer’s and will help refine the selection of candidates for therapeutic interventions most likely to benefit.

Source: EFE