New biomarker test detects early tau tangles in Alzheimer’s disease

Years before Tau Tangles appears in brain scans of patients with Alzheimer’s disease, a biomarker test developed at the University of Pittsburgh school or medicine can be small quantities of the clumping sensitive tau protein and the incorrectly folded pathological forms that have the brain lined, Cerebrospinal liquid detect and potentially blood, new research published today in Nature Medicine suggests.

The cerebrospinal liquid biomarker test correlates with the severity of cognitive decline, regardless of other factors, including brain amyloid deposition, which opened doors for diagnosis and intervention at an early stage.

Because amyloid-beta pathology often precedes the abnormalities of Tau in Alzheimer’s disease, most biomarker efforts are aimed at early detection of amyloid-beta changes. The clumping of Tau protein in well-ordered structures that are referred to by pathologists as “Neurofibrillary WirwarS “is a more determining event for Alzheimer’s disease because it is stronger associated with the cognitive changes that are seen in affected people.

Our test identifies very early stages of Tau Tangle formation -until a decade before Tau clonts can appear on a brain scan. Early detection is the key to more successful therapies for Alzheimer’s disease, since studies demonstrate that patients with little to no measurable tau sticks benefit more from new treatments than those with a considerable degree of tau brain deposits. “

Thomas Karikari, Ph.D., senior author, university professor of psychiatry at PITT

Since many older people who have amyloid-beta plaques in their brains, they will never develop cognitive symptoms of Alzheimer’s disease during their lives, they specify the widespread diagnostic framework developed by the Alzheimer’s Association the three neuropathological pillars needed to the Illness to diagnose-coincaminated-combed to diagnose the disease-coincaminated to diagnose the disease to diagnose the disease to diagnose the disease to diagnose-coveted to the disease te to the disease Diagnosting-combined to diagnose the disease combined to diagnose the disease-combined presence of tau and amyloid-beta pathology and neurodegeneration. In a search for early and accessible biomarkers for Alzheimer’s disease, the earlier work of Karikari showed that a brain-specific form of Tau, called BD-Tau, can be measured in blood and reliably the presence of Alzheimer’s disease-specific neurodegeneration can indicate . A few years earlier, Karikari showed that specific forms of fosphorylated Tau, P-TAU181, P-TAU217 and P-TAU212 in the blood can predict the presence of brain amyloid-beta without the need for precious and time-consuming brain image.

But these tools largely detect amyloid pathology, so the issue of early detection from Tau is still looming. Although Tau-Pet remains a reliable and accurate predictor of the tau load in the brain, the usefulness of the test is limited by availability, low resolution, high costs, labor and sensitivity. At present, Tau-Pet scans can only pick up the signal of neurofibrillary tangles when a large number is present in the brain, at which point the degree of brain pathology has become pronounced and is not easy to reversible.

In the latter study, using the tools of biochemistry and molecular biology, Karikari and team identified a core area of ​​the Tau protein needed for neurofibrillary jumble formation. Detecting places in that core area of ​​111 amino acids, a order they call Tau_258-368“ Can identify lumps-sensitive Tau proteins and help in initiating further diagnostics and early treatment. In particular, the two new phosphorylassing places, P-TAU-262 and P-TAU-356, the status of TAU aggregation at an early stage can accurately inform that, with an appropriate intervention, could possibly be reversed.

“Amyloid-beta is a production and Tau is a matchstick. A large percentage of people with brain amyloid-beta deposits will never develop dementia. But as soon as the tau sounds on a brain scan, it may be too late to place the fire and their Cognitive health can deteriorate quickly, “said Karikari. “Early detection of maze -sensitive Tau could identify the people who will probably develop the associated cognitive decline of Alzheimer’s and can be helped with new generation therapies.”

Other authors of this study are Eric Abrahamson, Ph.D., Xuemei Zeng, Ph.D., Anuradha Sehrawat, Ph.D., Yijun Chen, MS, Tharick Pascoal, MD, Ph.D. and Milos Ikonomovic, MD, all from Pitt; Tohidul Islam, Ph.D., Przemysław Kac, MS, Hlin Kvartsberg, Ph.D., Maria Olsson, BS, Emma Sjons, BS, Fernando Gonzalez-Sortiz, MS, Henrik Zetterberg, MD, Ph.D. and Kaj Blennow, MD, Ph.D., all from the University of Gothenburg, Sweden; Emily Hill, Ph.D., Ivana del Popolo, MS, Abbie Richardson, MS, Victoria Mitchell, MS and Mark Wall, Ph.D., All University of Warwick, VK; Stijn Servaes, Ph.D., Joseph Therriault, Ph.D., Cécile Tissot, Ph.D., Nesrine Rahmouni, MS and Pedro Rosa-Neto, MD, Ph.D., All of McGill University, Canada; Denis Smirnov, Ph.D. and Douglas Galasko, MD, both from the University of California, San Diego; Tammaryn Lashley, Ph.D., from University College London, UK.

This study was supported by, among others, the National Institute on Aging (Grants R0183874, U24AG082930, P30AG066468, RF1AG0525-01A1, R01AG05395, R37AG0235, RF1AG051AGE 1 AGAG07536, R01 AGAG07536, R01 AGAG07536, R01AD01AD01AD01 AGAG07536, R01AD016, R01AD016, R01AD01AD01AD01AD01AD01 AGAG07536, R01AD01ADOS07536, R01AD01AD01AD01AF 1AG072641, POUT1449 4), The Alzheimer’s Association (Grant Aarf-21-850325), the Swedish Alzheimer Foundation, the Aina (Ann) Wallströms and Mary-Ann Sjöbloms Foundation, The Emil and Waa Cornells Foundation and a professional violation fund from Fund Fund The Psychiatry Department, University of Pittsburgh.