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New Biomarkers Catch Tau Before It Tangles | ALZFORUM Tau pathology in humans or animals, without fail, is made up of the hyperphosphorylated protein In AD tau is hyperphosphorylated sub-stoichiometrically at multiple sites by several combinations of protein kinases Six isoforms of tau in the human brain and hyperphosphorylation at multiple sites in AD generate numerous protein species
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
ApoE3 Christchurch Clings Tightly to Tau, Averting Tangles The authors argue that tight binding between ApoE3Ch and tau that prevents fragmentation, plus weak binding between ApoE3Ch and lipoprotein receptor-related protein 1 (LRP1) and heparan sulfate proteoglycans, as reported previously, together prevent ApoE3Ch-bound tau from getting into neurons or microglia, stopping the spread of tau toxicity
Widely Used Tau Seeding Assay Challenged - ALZFORUM Unlabeled tau fragments aggregated readily, while C-terminally tagged tau formed only a third as many aggregates, and N-terminally tagged tau formed none Electron microscopy revealed that C-terminally labeled tau aggregated into short fibrils, about twice as thick as those generated by unlabeled tau, with a distinct appearance from PHFs
Heavyweight Tau Snuffs Out Hippocampal Bursts | ALZFORUM Shushed by Tau Left: In patch-clamp setup, tau from AD brain is loaded into the recording pipette and diffuses into the CA1 neuron with which the pipette has made its seal Middle: Immunofluorescence image showing successful delivery of tau, with biocytin (green) marking the neuron, Tau-13 antibody staining infused tau (red)
Tau (CP-13) - ALZFORUM CP-13 immunotherapy has been tested in disease models, with limited success Passive immunization of JNPL3 mice, which express human tau with the P301L mutation, prevented the appearance of pathological forms of tau, although this effect depended upon the brain region and tau fraction examined (d’Abramo et al , 2015)
Mouse Tau Knock-Ins: A Tale of Two Pathologies | ALZFORUM The former hyperphosphorylates tau but seeds no aggregates, while the latter hypophosphorylates tau initially, seeds aggregates, and later makes fibrils Duff suspects these pathways converge as the mice age, whereby the hyperphosphorylated tau eventually forms aggregates and tangles, whereas the seed-competent models eventually become
Tau PET as Progression Marker: It’s the Spread, Not the Brightness Tau PET scans in the TRIAD cohort were done with MK-6240, those in ADNI with the less-sensitive tracer flortaucipir (To compare this to disease staging by tau fluid biomarkers, see Part 7 of this series ) In the TRIAD cohort, a tau PET signal in the medial temporal lobe predicted accumulation in both Braak I-II and III-IV over the next two years
THY-Tau22 - ALZFORUM THY-Tau22 mice are a model for tau aggregation, a pathological hallmark of Alzheimer's disease as well as numerous tauopathies With age these mice develop a variety of tau-related neuropathological changes, including tau hyperphosphorylation, neurofibrillary-like tau inclusions, and ghost tangles
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