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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
ALS or Alzheimer’s? Blood Phospho-Tau Could Mean Either While numerous studies suggest p-tau217 and other p-tau forms possess enhanced specificity for CNS amyloid pathology, it remains crucial to consider the potential influence of other biological processes in both the CNS and PNS, which can modulate the activity of kinases and phosphatases on tau and, consequently, p-tau relative abundance and
LY3954068 | ALZFORUM As such, LY3954068 is designed to reduce the levels of tau protein This strategy assumes that decreasing the abundance of tau will slow the formation of tau aggregates and progression of tau pathology LY3954068 is being studied for the treatment of neurodegenerative diseases No preclinical work is published on LY3954068
Heavy 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 (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
Tau Modification Drugs Take a Hit with Negative Trial The rationale behind small-molecule OGA inhibition is that these drugs will decrease tau hyperphosphorylation and aggregation into neurofibrillary tangles (right) [Courtesy of Eli Lilly Co ] In his October 30 CTAD presentation, Lilly’s Adam Fleisher showed that ceperognastat missed its secondary outcome of reducing clinical symptoms in
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
Night-Night, Neurodegeneration: Sleep Aid Lulls Tau Pathology A different sleep drug, the GABA A modulator zolpidem, had no such effect, with mice bearing the full brunt of tau pathology (image below) Females, whose atrophy was milder, reaped little benefit from either therapy Goodnight, Degeneration: Vehicle-treated P301S E4 mouse show tau’s toll: swollen ventricles and a thinned hippocampus (left
Organization of Aβ Plaques and Tau Tangles Illuminated in AD Brain By contrast, tau aggregates were neatly ordered, with uniform, evenly spaced fibrils arranged into bundles Many of these tau filaments resembled the paired helical filaments characteristic of AD But surprisingly, others looked more like fibrils found in people with chronic traumatic encephalopathy (CTE)
rTg(tauP301L)4510 - ALZFORUM T2 mice were then crossed with the CaMKIIα-tTA activator line to create bi-transgenic mice (designated rT2 T2 when homozygous for the MAPT P301L transgene) rT2 T2 mice express even more tau P301L than rTg4510 mice, yet neurodegeneration is delayed and tau pathology occurs later and is less extreme in rT2 T2 mice than in rTg4510 mice These