Years before TAU tangles appear in cerebral scans of patients with Alzheimer’s disease, a biomarker test developed at the Pittsburgh University Faculty of Medicine can detect small amounts of the Tau protein prone to groups and their poorly folded pathological forms that cover the brain and brain fluid, the brain fluid, and potentially blood, a new investigation published today in Nature Medicine suggests.
The cerebrospinal fluid biomarker test correlates with the severity of cognitive impairment, regardless of other factors, including the deposition of cerebral amyloid, thus opening the doors for the diagnosis and intervention of the early stage disease.
Since the amyloid-low pathology often precedes Tau’s abnormalities in Alzheimer’s disease, most biomarker efforts have focused on the early detection of beta amyloid changes. However, the grouping of the Tau protein in well -ordered structures mentioned by pathologists as “Neurofibrillar tandoS “is a more defining event for Alzheimer’s disease, since it is more strongly associated with the cognitive changes observed in affected people.
“Our test identifies the very early stages of Tau Tangle’s formation, up to a decade before any TAU group can appear in a brain scan,” said principal author Thomas Karikari, Ph.D., assistant professor of psychiatry at Pitt “Early detection is key to the most successful therapies for Alzheimer’s disease, since the trials show that patients with tau tau insoluble unquantifiable are more likely to benefit from new treatments than those with a significant degree of tau brain deposits” .
Since many older people who have beta amyloid plates in their brains will never develop cognitive symptoms of Alzheimer’s disease during their life, the widely adopted diagnostic framework developed by the Alzheimer’s association specifies the three neuropathological pillars necessary to diagnose the disease- Combined presence of pathology and neurodegeneration of Tau and amyloid-beet. In a search for early and accessible biomarkers for Alzheimer’s disease, Karikari’s previous work showed that a specific tau shape of the brain, called BD-tau, can be measured in the blood and reliably indicate the presence of specific neurodegeneration of Alzheimer’s disease. Several years before, Karikari showed that the specific forms of phosphorylated tau, p-tau181, p-tau217 and p-tau212, in the blood they can predict the presence of amyloid beta brain without the need for expensive brain images and that consume a lot of time .
But these tools greatly detect the amyloid pathology, so the problem of early detection of Tau still appears. While Tau-Pet remains a reliable and precise predictor of Tau’s load in the brain, the usefulness of the test is limited by availability, under resolution, high cost, labor and sensitivity. At present, Tau-Pet scans can collect the signal of neurofibrillary tangles only when a large number is present in the brain, at which time the degree of brain pathology has pronounced and is not easily reversible.
In this latest research, using the tools of biochemistry and molecular biology, karikari and team identified a central region of the Tau protein that is necessary for the formation of neurofibrillar tangles. Detection of sites within that central region of 111 amino acids, a sequence called Tau258-368You can identify TAU proteins prone to grouping and help start additional diagnoses and early treatment. In particular, the two new phosphorylation sites, P-TAU-262 and P-TAU-356, can accurately inform the status of Tau’s aggregation early that, with appropriate intervention, could be reversed.
“Amiloid-beet is a ignition, and Tau is a phosphorus. A large percentage of people who have cerebral amyloid deposits will never develop dementia. But once the Tau will get entangled in a brain scan, it can be too late to put Fire and its cognitive health can deteriorate quickly, “Karikari said. “The early detection of Tau prone to entangle could identify people who will probably develop cognitive deterioration associated with Alzheimer’s and could help themselves with new generation therapies.”
Other authors of this research 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 of Pitt; Tohidul Islam, Ph.D., Przemys? Aw Kac, MS, Hlin Kvartsberg, Ph.D., Maria Olsson, Bs, Emma Sjons, Bs, Fernando Gonzalez-Ortiz, MD, MS, Henrik Zetterberg, MD, Ph.D,., .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., the entire University of Warwick, the United Kingdom; Stijn Servaes, Ph.D., Joseph Therriault, Ph.D., Cécile Tissot, Ph.D., Nesrine Rahmouni, MS and Pedro Rosa-Neto, MD, Ph.D., the entire University of McGill, Canada; Denis Smirnov, Ph.D., and Douglas Galassko, MD, both from the University of California, San Diego; Tammaryn Lashley, Ph.D., by University College London, United Kingdom.
This study was supported by, among others, the National Institute on Aging (subsidies R01AG083874, U24AG082930, P30AG066468, RF1AG052525-01A1, R01AG053952, R37AG023651, RF1AG025516, R01AG0733333267, R01AT AG072 41, P01AG14449 and P01AG025204, among others), Swedish research council ( Grant 2021-03244), the Alzheimer’s Association (Grant AARF-21-850325), the Alzheimer Swedish Foundation, the AINA Foundation (ANN) Wallströms and Mary-Ann Sjöbloms, the EMIL Foundation and Wera Cornells and a Professor Elder Department of Psychiatry, University of Pittsburgh.