CHICAGO, Dec. 7 (Xinhua) -- A novel form of an Alzheimer's protein found in the fluid that surrounds the brain and spinal cord indicates what stage of the disease a person is in, and tracks with tangles of tau protein in the brain, according to a study from Washington University School of Medicine in St. Louis.
The so-called microtubule binding region tau (MTBR tau) in the cerebrospinal fluid is an insoluble piece of the tau protein, and the primary component of tau tangles. The researchers realized that specific MTBR tau species were enriched in the brains of people with Alzheimer's disease, and that measuring levels of the species in the cerebrospinal fluid that bathes the brain might be a way to gauge how broadly the toxic tangles have spread through the brain.
To do so, the researchers developed a new method based on using chemicals to purify tau out of a solution, followed by mass spectrometry.
Using this technique, the researchers analyzed cerebrospinal fluid from 100 people in their 70s. Thirty had no cognitive impairment and no signs of Alzheimer's; 58 had amyloid plaques with no cognitive symptoms, or with mild or moderate Alzheimer's dementia; and 12 had cognitive impairment caused by other conditions.
The researchers found that levels of a specific form, MTBR tau 243, in the cerebrospinal fluid were elevated in the people with Alzheimer's and that it increased the more advanced a person's cognitive impairment and dementia were.
The researchers verified their results by following 28 members of the original group over two to nine years. Half of the participants had some degree of Alzheimer's at the start of the study. Over time, levels of MTBR tau 243 significantly increased in the Alzheimer's disease group, in step with a worsening of scores on tests of cognitive function.
The gold standard for measuring tau in the living brain is a tau-PET brain scan. To see how their technique matched up to the gold standard, the researchers compared the amount of tau visible in brain scans of 35 people: 20 with Alzheimer's and 15 without, with levels of MTBR tau 243 in the cerebrospinal fluid. MTBR tau 243 levels were highly correlated with the amount of tau identified in the brain scan, suggesting that their technique accurately measured how much tau and therefore damage had accumulated in the brain.
Alzheimer's begins when a brain protein called amyloid starts forming plaques in the brain. During this amyloid stage, which can last two decades or more, people show no signs of cognitive decline. However, soon after tangles of tau begin to spread in the neurons, people start exhibiting confusion and memory loss, and brain scans show increasing atrophy of brain tissue.
The study is published Monday in the journal Brain. Enditem
