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1. Extracellular Tau Oligomers Damage the Axon Initial Segment by an Endogenous Tau‐Dependent Mechanism

   https://doi.org/10.1002/alz.078491  

   Best, Merci N; Lim, Yunu; Ferenc, Nina; Kim, Nayoung; Wang, Dora Bigler; Sharifi, Kamyar; Wasserman, Anna; McTavish, Sloane; Siller, Karsten; Jones, Marieke K; et al (December 2023, Alzheimer's & Dementia)

   Abstract BackgroundNeuronal polarity and synaptic connectivity are compromised in Alzheimer’s disease (AD) and other tauopathies. The axon initial segment (AIS) is a key structure for regulating polarity and functions of neurons. It occupies the first 20‐60 µm of the axon, comprises a diffusion barrier that segregates axon‐enriched from somatodendritic‐enriched molecules, and has a high concentration of voltage‐gated ion channels that generate action potentials. Extracellular amyloid‐β oligomers compromise AIS integrity. However, effects on the AIS of toxic tau species, including extracellular oligomers (xcTauOs) that spread tau pathology from neuron to neuron by a prion‐like process, whereas unknown. Therefore, we wanted to test the hypothesis that AIS structure is sensitive to xcTauOs. MethodPrimary cortical neurons derived from either wild type (WT), or tau knockout (KO) mice were exposed to xcTauOs or vehicle. Quantitative western blotting and immunofluorescence microscopy with an antibody against the AIS‐enriched protein TRIM46 was used to monitor effects on the AIS. The same methods were also used to compare TRIM46 and two other AIS proteins, ankyrin‐G and neurofascin‐186 in human hippocampal tissue obtained from AD and age‐matched non‐AD donors. ResultIn cultured WT, but not TKO neurons, xcTauOs cause a trend toward AIS shortening and reduce the concentration of the resident AIS protein, TRIM46, without affecting total TRIM46 levels. Lentiviral‐driven human tau expression in tau KO neurons rescues TRIM46 sensitivity to xcTauOs. In human AD hippocampus, AIS length and TRIM46 concentration within the AIS are reduced in neurons containing neurofibrillary tangles (NFTs), without affecting the overall protein levels of multiple resident AIS proteins. ConclusionThese collective findings demonstrate that in cultured neurons, xcTauOs cause partial AIS damage by a mechanism dependent on intracellular tau, thereby raising the possibility that AIS reduction in AD is caused by xcTauOs working in concert with endogenous neuronal tau. 

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2. A measurable angular distribution for $$ \overline{B}\to {D}^{* }{\tau}^{-}{\overline{v}}_{\tau } $$ ​decays.

   https://doi.org/https://doi.org/10.1007/JHEP07(2020)194  

   Bhubanjyoti Bhattacharya, Alakabha Datta (July 2020, Journal of high energy physics)

   null (Ed.)
3. Effective equidistribution and property $$(\tau )$$

   https://doi.org/10.1090/jams/930  

   Einsiedler, M.; Margulis, G.; Mohammadi, A.; Venkatesh, A. (January 2020, Journal of the American Mathematical Society)
4. Powers of Tau in Asynchrony

   https://doi.org/10.14722/ndss.2024.24733  

   Das, Sourav; Xiang, Zhuolun; Ren, Ling (January 2024, Internet Society)
5. Mechanical injuries of neurons induce tau mislocalization to dendritic spines and tau-dependent synaptic dysfunction

   https://doi.org/10.1073/pnas.2008306117  

   Braun, Nicholas J.; Yao, Katherine R.; Alford, Patrick W.; Liao, Dezhi (November 2020, Proceedings of the National Academy of Sciences)

   Chronic traumatic encephalopathy (CTE) is associated with repeated traumatic brain injuries (TBI) and is characterized by cognitive decline and the presence of neurofibrillary tangles (NFTs) of the protein tau in patients’ brains. Here we provide direct evidence that cell-scale mechanical deformation can elicit tau abnormalities and synaptic deficits in neurons. Using computational modeling, we find that the early pathological loci of NFTs in CTE brains are regions of high deformation during injury. The mechanical energy associated with high-strain rate deformation alone can induce tau mislocalization to dendritic spines and synaptic deficits in cultured rat hippocampal neurons. These cellular changes are mediated by tau hyperphosphorylation and can be reversed through inhibition of GSK3β and CDK5 or genetic deletion of tau. Together, these findings identify a mechanistic pathway that directly relates mechanical deformation of neurons to tau-mediated synaptic impairments and provide a possibly exploitable therapeutic pathway to combat CTE. 

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