Neuroscientists at the University of Virginia have found out how a toxic form of tau protein, which is known to form tangles in the brains of individuals suffering from Alzheimer’s and a number of other neurodegenerative diseases, spreads through the brain as the disease gets worse.
The tau protein is a contributing factor in the cognitive deterioration that is linked with certain disorders. The research shows what makes it build up and how it hurts neurons, which are nerve cells. New therapies for Alzheimer’s disease that prevent or postpone symptom onset or reduce disease progression after symptom onset may be developed using these discoveries.
The new study by UVA also helps in the development of blood tests to identify Alzheimer’s in its early stages, when it is in theory most treatable. The researchers discovered that antibodies used in blood tests to measure this toxic, chemically modified variant of tau known as “taupT217” may be readily tricked into identifying other proteins, therefore compromising test accuracy. Lucky for us, they also showed how to avoid this problem.
The latest study by Dr. George Bloom of UVA and colleagues is the most thorough analysis to date of where and how taupT217 builds up in the brain. The findings provide a critical understanding of how Alzheimer’s disease and maybe other neurological disorders known as “non-tauopathies” Alzheimer’s arise. These include chronic traumatic encephalopathy and Parkinson’s disease.
According to Bloom, “The past few years have witnessed exciting advances in early Alzheimer’s detection by measuring the amount of taupT217 in blood or cerebrospinal fluid, but until now almost nothing has been learned about what causes this type of tau to form in the brain or how it affects neuron health.
“Knowing what provokes taupT217 to build up in the brain and how it harms neurons provides new openings for therapeutic intervention.”
The “microtubules” that act as highways for carrying significant materials within the neurons that make up the brain’s circuitry are one of the many crucial structures that tau builds and maintains in a healthy brain. However, tau is chemically altered and misshaped in Alzheimer’s patients in a manner that prevents normal functioning and renders it toxic. Eventually, this results in the breakdown of neural circuitry and cell death, two events that explain the cognitive deterioration in Alzheimer’s disease.
The reasons why this happens have only been partly understood, but new study from UVA provides further details. For instance, the researchers discovered that by exposing cultured neurons to tau oligomers or clusters, they could cause taupT217 accumulation. These have long been thought to be a damaging factor in the development of the illness and are known to develop in the Alzheimer’s brain. Additionally, they discovered that taupT217’s chemical alteration significantly reduces tau’s capacity to adhere to microtubules, which may facilitate the formation of harmful oligomers.
In terms of immediate clinical value, Bloom said, “we hope that our findings about the challenge of antibody specificity for measuring taupT217 in blood will quickly resonate with companies that are striving to develop commercially available tests to identify Alzheimer’s patients years before symptoms become evident.”
Due to the fact that irreparable brain damage has already happened before to the onset of symptoms, reliable early identification is vital for the development of Alzheimer’s treatments.
Alzheimer’s disease is not straightforward since it “reflects a multidimensional breakdown of normal brain cells,” according to Bloom.
However, the greatest chance for someday curing this horrible illness rests in focusing study on the early mechanisms that transform normal brains into Alzheimer’s brains.
The results were published in the journal Alzheimer’s & Dementia.
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