New Biomarkers Catch Tau Before It Tangles | ALZFORUM Detecting toxic forms of tau before they weave into dense thickets of tangles could pave the way for earlier diagnosis and treatment of tauopathies, including Alzheimer’s disease In the February 10 Nature Medicine, researchers led by Thomas Karikari, University of Pittsburgh, unveil their
LY3954068 | ALZFORUM LY3954068 is a small interfering RNA (siRNA) that targets expression of the microtubule-associated binding protein tau No information is available about the makeup of LY3954068
Tau (PHF-1) | ALZFORUM Recognizes tau doubly phosphorylated at serines 396 and 404 Immunoreactivity seen in Alzheimer's disease and other tauopathies but not controls Used to assess the progression of tau pathology in human disease and in the brains of animal models of tauopathy Validated in knockout and cell-based assays
A Tale of Two T Cells—Slowing Tau Spread, Shredding White Matter With T cells sidelined in these CD8 knockouts, tau pathology went on the offensive By 30 weeks of age, phospho-tau had spread deeper into the brain than in CD8-intact controls (image below) Michal Schwartz of the Weizmann Institute of Science in Rehovot, Israel, noted that these findings run counter to conventional thinking
Better Diagnosis with Blood Test Detecting Only Tau Made in Brain In the December 27 Brain, Karikari reported that plasma concentration of these brain-derived forms of tau (BD-tau) tracked with cerebrospinal fluid markers of amyloid plaques and of neurofibrillary tangles, with postmortem plaque and tangle load, and with cognitive test scores better than plasma total tau and neurofilament light, the currently available blood markers of neurodegeneration
Cell-Based Assay Matches Tau Strains to Neuropathological Diagnosis Tau, Incorporated A library of tau mutants generated by alanine substitution (red residues, left), was transduced into biosensor cell lines containing pre-existing tau fibril strains The degree of incorporation of each mutant into the growing fibrils (middle) is measured via FRET (right) [Courtesy of Vaquer-Alicea et al , Science Advances
Widely Used Tau Seeding Assay Challenged - ALZFORUM Many research groups study tau misfolding and propagation using in vitro models, but interpreting findings from artificial systems can be dicey In a preprint on bioRxiv, researchers led by Eckhard Mandelkow at the German Center for Neurodegenerative Diseases, Bonn, question whether a widely used
JNJ-64042056 | ALZFORUM In both wild-type C57BL 6 and P301L mutant tau transgenic mice, a three-month regimen of subcutaneous ACI-35 injection rapidly generated high titers of polyclonal IgG antibodies specifically directed against phosphorylated tau, rather than non-phosphorylated tau The resulting antibodies were reported to bind neurofibrillary tangles in mouse brain tissue sections and to reduce soluble tau as
Tau (AT8); Phospho Tau (Ser 202, Thr 205) - ALZFORUM Hyperphosphorylated tau polymerizes into paired helical filaments, which aggregate to form neurofibrillary tangles, one of the defining lesions of Alzheimer’s disease Recognizes paired helical filament (PHF) tau Phosphorylation at serine 202 and threonine 205 is required for recognition by AT8
Triple Trouble: New Knock-in Turbocharges Tauopathy They accumulated hyperphosphorylated tau in their brains and lost synapses by approximately 15 months of age, but they had no tau oligomers capable of seeding aggregates Such “seeds” are a hallmark of human tauopathies Recognizing the need for models with more robust pathology at a younger age, the authors engineered the new triple-knock-ins