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In brief:

• A newly discovered blood marker, MTBR-tau243, can reveal how much Alzheimer’s disease pathology is present in the brain. The higher the level, the more extensive the pathology.
• This insight will be critical in distinguishing whether a patient’s symptoms are due to Alzheimer’s disease or another condition. It will also help identify individuals most likely to benefit from the new drugs approved in countries such as the US, Japan and China – with approvals anticipated soon in Europe.

The study was co-led by Professor Oskar Hansson of �۶���Ƶ and Professor Randall J. Batemanof Washington University School of Medicine. Together, they identified MTBR-tau243, a protein that indicates the level of Alzheimer’s disease in the brain. The discovery could significantly enhance diagnostic accuracy in clinical practice and aid in evaluating the effectiveness of Alzheimer’s treatments.

�۶���Ƶ had previously shown that the biomarker P-tau217 can detect Alzheimer’s disease up to 20 years before symptoms appear. However, this marker does not reflect how far the disease has progressed. As a result, a patient with cognitive symptoms who tests positive for P-tau217 may be diagnosed with Alzheimer’s even if their current symptoms are due to another cause – although they might develop Alzheimer’s symptoms later.

“This could pose major challenges for patients,” explains Professor Hansson. “That’s why researchers have been searching for a blood marker that appears later in the disease course, when symptoms are more pronounced. We’ve now identified MTBR-tau243 as exactly such a marker – one that also provides a clearer picture of how advanced the disease is in the brain. This is the first time such a marker has been measurable in blood. The higher its levels, the more advanced the Alzheimer’s pathology.”

A two-step approach for diagnosis and treatment planning

Looking ahead, P-tau217 and MTBR-tau243 could be used in combination in clinical settings. First, P-tau217would help determine whether a patient has Alzheimer-related changes in the brain. If the result is positive, MTBR-tau243 could then confirm whether the patient’s current symptoms are indeed due to Alzheimer’s disease, or possibly another condition.

These tests will be essential for the global rollout of disease-modifying treatments for Alzheimer’s. That said, a thorough clinical evaluation by a physician will always be necessary before initiating any treatment, emphasises Professor Hansson.

“This blood test clearly identifies Alzheimer’s tau tangles, which is our best biomarker measure of Alzheimer’s symptoms and dementia,” said co-senior author Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology at WashU Medicine.

“In our clinical practice right now, we don’t have easy or accessible measures of Alzheimer’s tangles and dementia, and so a tangle blood test like this can provide a much better indication if the symptoms are due to Alzheimer’s and may also help doctors decide which treatments are best for their patients.”