Alzheimer’s Disease Monitored By Novel Biomarker

Discovery of an Alzheimer's disease (AD) protein biomarker – microtubule-binding region tau (MTBR tau) found in the cerebrospinal fluid, the fluid that surrounds the brain and spinal cord, can measure the levels of tau tangles in the brain. This allows monitoring the different stages of the disease as per a study from researchers at Washington University School of Medicine in St. Louis, published in the journal Brain. Alzheimer’s disease is a neurodegenerative disease characterized by a decline in memory and cognition due to the formation of beta-amyloid plaques followed by tau tangles in the brain tissue. These brain changes can appear long before the actual symptoms occur.

"If we can translate this into the clinic, we'd have a way of knowing whether a person's symptoms are due to tau pathology in Alzheimer's disease and where they are in the disease course, without needing to do a brain scan. As a physician, this information is invaluable in informing patient care, and in the future, to guide treatment decisions", said senior author Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology.MTBR tau is the primary insoluble component of tau tangles.

The Novel Biomarker:

The team analyzed cerebrospinal fluid from 100 people in their 70s. 30 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. It was observed that a particular species of the biomarker -- MTBR tau 243 were elevated in the cerebrospinal fluid of AD patients, much higher in the more advanced form of the disease.

The result was verified as 28 members of the original group who were on follow-up for two to nine years, revealed a significant increase in the levels of MTBR tau 243. These changes correlated with the cognitive dysfunction. Similarly, the amount of tau visible in the gold standard technique – tau-PET brain scan matched with the levels of MTBR tau 243 in the cerebrospinal fluid in 35 people – 20 with and 15 without Alzheimer's disease.

"What we've found here is that a novel form of tau, MTBR tau 243, increases continuously as tau pathology progresses.This could be a way for us to not only diagnose Alzheimer's disease but tell where people are in the disease. We also found some specific MTBR tau species in the space between neurons in the brain, which suggests that they may be involved in spreading tau tangles from one neuron to another. That finding opens up new windows for novel therapeutics for Alzheimer's disease based on targeting MTBR tau to stop the spread of tangles", said the first author Kanta Horie, Ph.D., a visiting scientist in Bateman's lab.

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Facts on Alzheimer's disease:

• More than 5 million Americans of all ages have Alzheimer's.
• An estimated 5.8 million Americans age 65 and older are living with Alzheimer's dementia in 2020.
• Eighty percent are age 75 or older.
• One in 10 people age 65 and older (10%) has Alzheimer's dementia.

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Source-Medindia