keyword
https://read.qxmd.com/read/38528629/overlaps-and-divergences-between-tauopathies-and-synucleinopathies-a-duet-of-neurodegeneration
#1
REVIEW
Wen Li, Jia-Yi Li
Proteinopathy, defined as the abnormal accumulation of proteins that eventually leads to cell death, is one of the most significant pathological features of neurodegenerative diseases. Tauopathies, represented by Alzheimer's disease (AD), and synucleinopathies, represented by Parkinson's disease (PD), show similarities in multiple aspects. AD manifests extrapyramidal symptoms while dementia is also a major sign of advanced PD. We and other researchers have sequentially shown the cross-seeding phenomenon of α-synuclein (α-syn) and tau, reinforcing pathologies between synucleinopathies and tauopathies...
March 26, 2024: Translational Neurodegeneration
https://read.qxmd.com/read/38528167/inferring-parameters-of-pyramidal-neuron-excitability-in-mouse-models-of-alzheimer-s-disease-using-biophysical-modeling-and-deep-learning
#2
JOURNAL ARTICLE
Soheil Saghafi, Timothy Rumbell, Viatcheslav Gurev, James Kozloski, Francesco Tamagnini, Kyle C A Wedgwood, Casey O Diekman
Alzheimer's disease (AD) is believed to occur when abnormal amounts of the proteins amyloid beta and tau aggregate in the brain, resulting in a progressive loss of neuronal function. Hippocampal neurons in transgenic mice with amyloidopathy or tauopathy exhibit altered intrinsic excitability properties. We used deep hybrid modeling (DeepHM), a recently developed parameter inference technique that combines deep learning with biophysical modeling, to map experimental data recorded from hippocampal CA1 neurons in transgenic AD mice and age-matched wildtype littermate controls to the parameter space of a conductance-based CA1 model...
March 25, 2024: Bulletin of Mathematical Biology
https://read.qxmd.com/read/38527450/cerebral-tau-deposition-in-co-morbid-progressive-supranuclear-palsy-and-amyotrophic-lateral-sclerosis-an-18f-flortaucipir-and-7t-mri-study
#3
JOURNAL ARTICLE
Ian Cheong, Yong Du, Gwenn Smith, Jun Hua, Xu Li, Alexander Pantelyat
Introduction Progressive supranuclear palsy (PSP) is a four-repeat tauopathy characterized by multiple clinicopathologic subtypes. Advanced neuroimaging techniques have shown an early ability to distinguish PSP subtypes non-invasively for improved diagnosis. This study utilized tau-PET imaging and MRI techniques at 7 Tesla (7T) to determine the neuroimaging profile of a participant with comorbid PSP and amyotrophic lateral sclerosis (ALS). Method [18F]-flortaucipir PET imaging was performed on one participant with PSP-ALS, one participant with typical PSP (Richardson's syndrome; PSP-RS), and 15 healthy control volunteers...
March 25, 2024: Neuro-degenerative Diseases
https://read.qxmd.com/read/38526799/loss-of-tmem106b-exacerbates-tau-pathology-and-neurodegeneration-in-ps19-mice
#4
JOURNAL ARTICLE
Tuancheng Feng, Huan Du, Cha Yang, Ya Wang, Fenghua Hu
TMEM106B, a gene encoding a lysosome membrane protein, is tightly associated with brain aging, hypomyelinating leukodystrophy, and multiple neurodegenerative diseases, including frontotemporal lobar degeneration with TDP-43 aggregates (FTLD-TDP). Recently, TMEM106B polymorphisms have been associated with tauopathy in chronic traumatic encephalopathy (CTE) and FTLD-TDP patients. However, how TMEM106B influences Tau pathology and its associated neurodegeneration, is unclear. Here we show that loss of TMEM106B enhances the accumulation of pathological Tau, especially in the neuronal soma in the hippocampus, resulting in severe neuronal loss in the PS19 Tau transgenic mice...
March 25, 2024: Acta Neuropathologica
https://read.qxmd.com/read/38526616/tmem106b-coding-variant-is-protective-and-deletion-detrimental-in-a-mouse-model-of-tauopathy
#5
JOURNAL ARTICLE
George A Edwards, Caleb A Wood, Yang He, Quynh Nguyen, Peter J Kim, Ruben Gomez-Gutierrez, Kyung-Won Park, Yong Xu, Cody Zurhellen, Ismael Al-Ramahi, Joanna L Jankowsky
TMEM106B is a risk modifier of multiple neurological conditions, where a single coding variant and multiple non-coding SNPs influence the balance between susceptibility and resilience. Two key questions that emerge from past work are whether the lone T185S coding variant contributes to protection, and if the presence of TMEM106B is helpful or harmful in the context of disease. Here, we address both questions while expanding the scope of TMEM106B study from TDP-43 to models of tauopathy. We generated knockout mice with constitutive deletion of TMEM106B, alongside knock-in mice encoding the T186S knock-in mutation (equivalent to the human T185S variant), and crossed both with a P301S transgenic tau model to study how these manipulations impacted disease phenotypes...
March 25, 2024: Acta Neuropathologica
https://read.qxmd.com/read/38520489/disentangling-and-quantifying-the-relative-cognitive-impact-of-concurrent-mixed-neurodegenerative-pathologies
#6
JOURNAL ARTICLE
Carolina Maldonado-Díaz, Satomi Hiya, Raquel T Yokoda, Kurt Farrell, Gabriel A Marx, Justin Kauffman, Elena V Daoud, Mitzi M Gonzales, Alicia S Parker, Leyla Canbeldek, Lakshmi Shree Kulumani Mahadevan, John F Crary, Charles L White, Jamie M Walker, Timothy E Richardson
Neurodegenerative pathologies such as Alzheimer disease neuropathologic change (ADNC), Lewy body disease (LBD), limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and cerebrovascular disease (CVD) frequently coexist, but little is known about the exact contribution of each pathology to cognitive decline and dementia in subjects with mixed pathologies. We explored the relative cognitive impact of concurrent common and rare neurodegenerative pathologies employing multivariate logistic regression analysis adjusted for age, gender, and level of education...
March 23, 2024: Acta Neuropathologica
https://read.qxmd.com/read/38517786/caloric-restriction-improves-spatial-learning-deficits-in-tau-mice
#7
JOURNAL ARTICLE
Valeria Cogut, Taylor L McNeely, Tyler J Bussian, Sara I Graves, Darren J Baker
BACKGROUND: Caloric restriction (CR) has been recognized for its benefits in delaying age-related diseases and extending lifespan. While its effects on amyloid pathology in Alzheimer's disease (AD) mouse models are well-documented, its effects on tauopathy, another hallmark of AD, are less explored. OBJECTIVE: To assess the impact of a short-term 30% CR regimen on age-dependent spatial learning deficits and pathological features in a tauopathy mouse model. METHODS: We subjected male PS19 tau P301S (hereafter PS19) and age-matched wildtype mice from two age cohorts (4...
March 19, 2024: Journal of Alzheimer's Disease: JAD
https://read.qxmd.com/read/38514176/clinicoradiological-and-neuropathological-evaluation-of-primary-progressive-aphasia
#8
JOURNAL ARTICLE
Dror Shir, Nick Corriveau-Lecavalier, Camilo Bermudez Noguera, Leland Barnard, Nha Trang Thu Pham, Hugo Botha, Joseph R Duffy, Heather M Clark, Rene L Utianski, David S Knopman, Ronald C Petersen, Bradley F Boeve, Melissa E Murray, Aivi T Nguyen, R Ross Reichard, Dennis W Dickson, Gregory S Day, Walter K Kremers, Neill R Graff-Radford, David T Jones, Mary M Machulda, Julie A Fields, Jennifer L Whitwell, Keith A Josephs, Jonathan Graff-Radford
BACKGROUND: Primary progressive aphasia (PPA) defines a group of neurodegenerative disorders characterised by language decline. Three PPA variants correlate with distinct underlying pathologies: semantic variant PPA (svPPA) with transactive response DNA-binding protein of 43 kD (TDP-43) proteinopathy, agrammatic variant PPA (agPPA) with tau deposition and logopenic variant PPA (lvPPA) with Alzheimer's disease (AD). Our objectives were to differentiate PPA variants using clinical and neuroimaging features, assess progression and evaluate structural MRI and a novel 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) image decomposition machine learning algorithm for neuropathology prediction...
March 21, 2024: Journal of Neurology, Neurosurgery, and Psychiatry
https://read.qxmd.com/read/38513667/p-tau217-correlates-with-neurodegeneration-in-alzheimer-s-disease-and-targeting-p-tau217-with-immunotherapy-ameliorates-murine-tauopathy
#9
JOURNAL ARTICLE
Denghong Zhang, Wei Zhang, Chen Ming, Xuheng Gao, Huilong Yuan, Xiaojie Lin, Xinru Mao, Chunping Wang, Xiaoyi Guo, Ying Du, Lin Shao, Renzhi Yang, Zhihao Lin, Xilin Wu, Timothy Y Huang, Zhanxiang Wang, Yun-Wu Zhang, Huaxi Xu, Yingjun Zhao
Neuronal loss is the central issue in Alzheimer's disease (AD), yet no treatment developed so far can halt AD-associated neurodegeneration. Here, we developed a monoclonal antibody (mAb2A7) against 217 site-phosphorylated human tau (p-tau217) and observed that p-tau217 levels positively correlated with brain atrophy and cognitive impairment in AD patients. Intranasal administration efficiently delivered mAb2A7 into male PS19 tauopathic mouse brain with target engagement and reduced tau pathology/aggregation with little effect on total soluble tau...
March 12, 2024: Neuron
https://read.qxmd.com/read/38512690/studying-microtubule-dynamics-in-human-neurons-two-dimensional-microtubule-tracing-and-kymographs-in-ipsc-and-sh-sy5y-derived-neurons-for-tau-research
#10
JOURNAL ARTICLE
Nadine Allroggen, Helen Breuer, Sarah Bachmann, Michael Bell, Hans Zempel
The study of microtubule (MT) dynamics is essential for the understanding of cellular transport, cell polarity, axon formation, and other neurodevelopmental mechanisms. All these processes rely on the constant transition between assembly and disassembly of tubulin polymers to/from MTs, known as dynamic instability. This process is well-regulated, among others, by phosphorylation of microtubule-associated proteins (MAP), including the Tau protein. Protein kinases, in particular the microtubule affinity regulating kinase (MARK), regulate the MT-Tau interaction, inducing Tau dissociation by phosphorylation...
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38512688/cultivation-differentiation-and-lentiviral-transduction-of-human-induced-pluripotent-stem-cell-hipsc-derived-glutamatergic-neurons-for-studying-human-tau
#11
JOURNAL ARTICLE
Sarah Buchholz, Michael Bell-Simons, Cagla Cakmak, Jennifer Klimek, Li Gan, Hans Zempel
Tau pathology is a major hallmark of many neurodegenerative diseases summarized under the term tauopathies. In most of these disorders,  such as Alzheimer's disease, the neuronal axonal microtubule-binding Tau protein becomes mislocalized to the somatodendritic compartment. In human disease, this missorting of Tau is accompanied by an abnormally high phosphorylation state of the Tau protein, and several downstream pathological consequences (e.g., loss of microtubules, degradation of postsynaptic spines, impaired synaptic transmission, neuronal death)...
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38512687/differentiating-sh-sy5y-cells-into-polarized-human-neurons-for-studying-endogenous-and-exogenous-tau-trafficking-four-protocols-to-obtain-neurons-with-noradrenergic-dopaminergic-and-cholinergic-properties
#12
JOURNAL ARTICLE
Felix Langerscheidt, Michael Bell-Simons, Hans Zempel
Pathological alterations of the neuronal Tau protein are characteristic for many neurodegenerative diseases, called tauopathies. To investigate the underlying mechanisms of tauopathies, human neuronal cell models are required to study Tau physiology and pathology in vitro. Primary rodent neurons are an often used model for studying Tau, but rodent Tau differs in sequence, splicing, and aggregation propensity, and rodent neuronal physiology cannot be compared to humans. Human-induced pluripotent stem cell (hiPSC)-derived neurons are expensive and time-consuming...
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38512677/differential-regulation-of-neurotrophic-factors-during-pathogenic-tau-aggregation-in-a-tau-transgenic-mouse-model-for-alzheimer-s-disease-a-protocol-for-double-labeling-mrna-by-in-situ-hybridization-and-protein-epitopes-by-immunohistochemistry
#13
JOURNAL ARTICLE
Katharina Schindowski
Alzheimer's disease (AD), most tauopathies, and other neurodegenerative diseases are highly associated to impaired neurotrophin regulation and imbalanced neurotrophin transport and distribution. Neurotrophins are crucial for the survival and maintenance of distinct neuronal population therefore their supply is essential for a healthy brain. Tau phosphorylation occurs at different sites of the tau protein and some phospho-epitopes are highly associated to AD (e.g., abnormally phosphorylated tau at Thr212/Ser214)...
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38512674/methods-for-biochemical-isolation-of-insoluble-tau-in-rodent-models-of-tauopathies
#14
JOURNAL ARTICLE
Geoffrey Canet, Emma Rocaboy, Sofia Diego-Diàz, Robert A Whittington, Carl Julien, Emmanuel Planel
The intracellular accumulation of microtubule-associated protein tau is a characteristic feature of tauopathies, a group of neurodegenerative diseases including Alzheimer's disease. Formation of insoluble tau aggregates is initiated by the abnormal hyperphosphorylation and oligomerization of tau. Over the past decades, multiple transgenic rodent models mimicking tauopathies have been develop, showcasing this neuropathological hallmark. The biochemical analysis of insoluble tau in these models has served as a valuable tool to understand the progression of tau-related pathology...
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38512673/western-blot-of-tau-protein-from-mouse-brains-extracts-how-to-avoid-signal-artifacts
#15
JOURNAL ARTICLE
Parissa Fereydouni-Forouzandeh, Geoffrey Canet, Sofia Diego-Diàz, Emma Rocaboy, Serena Petry, Robert A Whittington, Emmanuel Planel
Tau is a microtubule-associated protein enriched in the axonal compartment. Its most well-known function is to bind and stabilize microtubules. In Alzheimer's disease and other neurodegenerative diseases known as tauopathies, tau undergoes several abnormal post-translational modifications including hyperphosphorylation, conformational changes, oligomerization, and aggregation. Numerous mouse models of tauopathies have been developed, and Western blotting remains an invaluable tool in studying tau protein physiological and pathological changes in these models...
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38512672/phosphorylation-of-tau-protein-by-cdk2-cyclin-a-and-gsk3%C3%AE-recombinant-kinases-analysis-of-phosphorylation-patterns-by-nuclear-magnetic-resonance-spectroscopy
#16
JOURNAL ARTICLE
Léa El Hajjar, Clarisse Bridot, Marine Nguyen, François-Xavier Cantrelle, Isabelle Landrieu, Caroline Smet-Nocca
Posttranslational modifications (PTMs) of proteins can be investigated by Nuclear Magnetic Resonance (NMR) spectroscopy as a powerful analytical tool to define modification sites, their relative stoichiometry, and crosstalk between modifications. As a Structural Biology method, NMR provides important additional information on changes in protein conformation and dynamics upon modification as well as a mapping of binding sites upon biomolecular interactions. Indeed, PTMs not only mediate functional modulation in protein-protein interactions, but can also induce diverse structural responses with different biological outcomes...
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38512671/the-o-glcnac-modification-of-recombinant-tau-protein-and-characterization-of-the-o-glcnac-pattern-for-functional-study
#17
JOURNAL ARTICLE
Léa El Hajjar, Clarisse Bridot, Marine Nguyen, François-Xavier Cantrelle, Isabelle Landrieu, Caroline Smet-Nocca
The neuronal microtubule-associated tau protein is characterized in vivo by a large number of post-translational modifications along the entire primary sequence that modulates its function. The primary modification of tau is phosphorylation of serine/threonine or tyrosine residues that is involved in the regulation of microtubule binding and polymerization. In neurodegenerative disorders referred to as tauopathies including Alzheimer's disease, tau is abnormally hyperphosphorylated and forms fibrillar inclusions in neurons progressing throughout different brain area during the course of the disease...
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38512670/quantification-of-methylation-and-phosphorylation-stoichiometry
#18
JOURNAL ARTICLE
Christopher A Ayoub, Khadijah I Moore, Jeff Kuret
Tauopathies including Alzheimer's disease (AD) are neurodegenerative disorders accompanied by the conversion of functional forms of the microtubule associated protein Tau into non-functional aggregates. A variety of post-translational modifications (PTMs) on Tau precede or accompany the conversion, placing them in position to modulate Tau function as well as its propensity to aggregate. Although Tau PTMs can be characterized by their sites of modification, their total stoichiometry when summed over all sites also is an important metric of their potential impact on function...
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38512662/assays-for-the-screening-and-characterization-of-tau-aggregation-inhibitors
#19
JOURNAL ARTICLE
David Horsley, Janet E Rickard, Thomas Vorley, Matilda F Leeper, Claude M Wischik, Charles R Harrington
Aggregation of tau protein is a pathological hallmark of Alzheimer's disease and other neurodegenerative tauopathies. Inhibition of tau aggregation may provide a method for treatment of these disorders. Methods to identify tau aggregation inhibitors (TAIs) in vitro are useful and here we describe assays for TAIs using purified recombinant tau protein fragments in a cell-free immunoassay format and in a stably transfected cell model to create a more physiological environment.
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38512658/characterization-of-posttranslationally-modified-phf-1-tau-peptides-using-gaussian-accelerated-molecular-dynamics-simulation
#20
JOURNAL ARTICLE
Tabassum Khair Barbhuiya, Dulari K Jayarathna, Raechelle Gilmour, Caroline Smet-Nocca, Neha S Gandhi
The microtubule-associated protein, Tau, is an intrinsically disordered protein that plays a crucial role in neurodegenerative diseases like Alzheimer's disease. The posttranslational modifications across the Tau protein domains are involved in regulating Tau protein's function and disease onset. Of the various posttranslational modifications at Ser, Thr, and Tyr sites, O-GlcNAcylation and phosphorylation are the most critical ones, playing a vital role in Tau aggregation and tauopathies. To understand the function, it is essential to characterize the structural changes associated with Tau modification...
2024: Methods in Molecular Biology
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