Brain Science

The Brain Change that Predicts Alzheimer’s Disease

The Brain Change that Predicts Alzheimer’s Disease about undefined
The latest research points to a new hallmark of Alzheimer's disease that could prove to be far more promising as an early marker of the malady than the often talked about tau tangles and amyloid plaques. Detecting this marker when it first develops could provide the earliest indicator of the disease, as it can be found as much as ten to 20 years before the first symptoms appear. I’m talking about something called reactive astrogliosis. Reactive astrogliosis is a fancy term for a regenerative process that certain brain cells, called astrocytes, go through when the body’s central nervous system suffers injury or disease. To understand reactive astrogliosis, you have to know more about the different kinds of cells in the brain, starting with neurons. Neurons are the basic working units of the brain, receiving and transmitting information via electrical signals. In Alzheimer's disease, this ability to communicate gets disrupted leading to loss of function and cell death. But neurons don't function alone. They work with other brain cells that don't produce electrical signals; the main type is the glial cell. Over half the cells in the brain are glial cells, and these are divided into various sub-types that have specialist functions. One such sub-type is the astrocyte. Astrocytes are star-shaped cells that perform many vital functions in the central nervous system including balancing cellular energy. Astrocytes support neurons in their development and growth, help them form efficient connections with one another, monitor their signaling, balance their electrical impulses and feed nutrients to them. If the central nervous system is damaged or suffers injury or disease, this triggers a range of changes to astrocytes, enabling them to limit tissue damage, carry out repairs and restore balance. At its core, reactive astrogliosis is a positive thing, but that doesn’t mean all of its effects are good.

Happens Before Tau and Amyloid 

Researchers at the Karolinska Institute in Sweden have demonstrated that reactive astrogliosis comes before the other hallmarks of Alzheimer's, taking place during the initial stages of the disease. In its attempt to repair damage to the central nervous system, reactive astrogliosis upregulates the production of acidic proteins and promotes the release of inflammatory mediators to trigger and promote neuro-inflammation. The Swedish researchers describe this as "an early contributory driving force in Alzheimer's disease pathology." They've shown that reactive astrocytes are closely associated with the development of amyloid plaque and tau tangles in key memory areas of people with Alzheimer's. They've also demonstrated a high degree of reactive astrogliosis in patients with mild cognitive impairment (MCI) and in pre-symptomatic patients with an early-onset genetic form of Alzheimer's.

The Future of Alzheimer’s Treatment? 

Because astrocytes are so crucial to the development of early Alzheimer's, they provide a promising target for preclinical diagnosis and treatment. This led to the development of several tracers that light up astrocytes in positron emission tomography (PET) brain scans. However, the existing tracers don't provide the precision necessary to follow astrocytes’ role in Alzheimer’s development. So, the Swedish scientists tested a new tracer. They tested this tracer, called BU99008, in the brains of six people who died of Alzheimer's and seven people who died of other causes. Amit Kumar, first author of the study, explained their findings, saying, "Our study shows that BU99008 can detect important reactive astrocytes with good selectivity and specificity, making it a potentially important clinical astrocytic PET tracer. "The results can improve our knowledge of the role played by reactive astrogliosis in Alzheimer's disease." Principal investigator and professor of clinical neuroscience, Agneta Nordberg, added, "As far as we can judge, this is the first time that BU99008 could visualize reactive astrogliosis in Alzheimer's disease brains. "The results can have broad clinical implications that cover other disorders of reactive astroglial dysfunction." Dr. Nordberg and the team published their report in the journal Molecular Psychiatry last April.
  1. https://www.nature.com/articles/s41380-021-01101-5 

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