New research has found that the accumulation of amyloid protein in the brain, a long-associated factor in Alzheimer’s disease, may not be enough to cause the symptoms and instead may require a biomarker in the blood. Researchers from the University of Pittsburgh School of Medicine conducted a study of 1,000 healthy elderly people and found that those who went on to develop Alzheimer’s had activated astrocyte immune cells indicated by a marker in the blood. The discovery that brain inflammation related to astrocytes may be the key regulator in the disease challenges the long-held theory that the build-up of amyloid protein is the determining factor in developing Alzheimer’s. This research suggests that screening for patients with both blood biomarkers of astrocyte reactivity and brain amyloid may be the optimal way to identify those most at risk of developing Alzheimer’s disease.
There are an estimated 50 million people worldwide who suffer from dementia, with two-thirds of dementia cases due to Alzheimer’s. Alzheimer’s is a fatal disease: most patients die within a decade of being diagnosed. However, there is a long pre-clinical stage during which time there are no symptoms of the disease, so the entire course of the disease can last up to 25 years. The study found that the biomarker GFAP, a marker of astrocyte reactivity in the blood, tied in with previous research conducted by Dr Tharick Pascoal’s team, suggesting that inflammation in the brain plays an important role in the progression of Alzheimer’s.
Astrocytes are immune cells in the brain that, like other glial cells, supply neurons with nutrients and oxygen essential for their survival. Dr Bruna Bellaver, the study’s first author, explains that astrocytes “co-ordinate” the relationship between brain amyloid and tau (another protein associated with Alzheimer’s) and that biomarkers like GFAP in glial cells, in general, are not considered in any main disease model. The new study helps to narrow down the patient pool for clinical drug trials focused on Alzheimer’s, which is useful given that drug trials are taking place at earlier stages of the disease’s progression.
Previously, many treatments focused on targeting amyloid plaques and tau tangles in the hope this would treat the disease. However, the study found that these treatments have provided no clinical benefits, and about one-third of cognitively normal older people have these plaques, suggesting that other factors are necessary for the condition to develop. In 2021, the US Food and Drug Administration approved a drug, aducanumab, marketed as Aduhelm, to treat Alzheimer’s, citing “substantial evidence” that it reduced beta-amyloid plaques. Despite this, some researchers said that there was insufficient evidence that the drug slowed disease progression.
In conclusion, while previous research has associated Alzheimer’s with amyloid plaque build-up in the brain, the new study by the University of Pittsburgh suggests that the accumulation of amyloid protein alone may not be enough to cause the onset of Alzheimer’s symptoms. Instead, biomarkers in the blood, specifically GFAP, that indicate activated astrocyte immune cells in the brain, must also be present. The discovery may help to create a new screening process for the disease and improve patient selection for future clinical drug trials.
