28,724 results match your criteria tau protein


Characterization of monomeric and soluble aggregated Aβ in Down's syndrome and Alzheimer's disease brains.

Neurosci Lett 2021 Apr 10:135894. Epub 2021 Apr 10.

Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

The major characteristics of Alzheimer's disease (AD) are amyloid plaques, consisting of aggregated beta amyloid (Aβ) peptides, together with tau pathology (tangles, neuropil treads and dystrophic neurites surrounding the plaques), in the brain. Down's syndrome (DS) individuals are at increased risk to develop AD-type pathology; most DS individuals have developed substantial pathology already at the age of 40. DS individuals have an extra copy of chromosome 21, harbouring the amyloid precursor protein gene (APP). Read More

View Article and Full-Text PDF

Tau aggregates are RNA-protein assemblies that mislocalize multiple nuclear speckle components.

Neuron 2021 Apr 7. Epub 2021 Apr 7.

Department of Biochemistry, University of Colorado, Boulder, CO, USA; Howard Hughes Medical Institute, University of Colorado, Boulder, CO, USA. Electronic address:

Tau aggregates contribute to neurodegenerative diseases, including frontotemporal dementia and Alzheimer's disease (AD). Although RNA promotes tau aggregation in vitro, whether tau aggregates in cells contain RNA is unknown. We demonstrate, in cell culture and mouse brains, that cytosolic and nuclear tau aggregates contain RNA with enrichment for small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs). Read More

View Article and Full-Text PDF

The Use, Standardization, and Interpretation of Brain Imaging Data in Clinical Trials of Neurodegenerative Disorders.

Authors:
Adam J Schwarz

Neurotherapeutics 2021 Apr 12. Epub 2021 Apr 12.

Takeda Pharmaceuticals Ltd., 40 Landsdowne Street, Cambridge, MA, 02139, USA.

Imaging biomarkers play a wide-ranging role in clinical trials for neurological disorders. This includes selecting the appropriate trial participants, establishing target engagement and mechanism-related pharmacodynamic effect, monitoring safety, and providing evidence of disease modification. In the early stages of clinical drug development, evidence of target engagement and/or downstream pharmacodynamic effect-especially with a clear relationship to dose-can provide confidence that the therapeutic candidate should be advanced to larger and more expensive trials, and can inform the selection of the dose(s) to be further tested, i. Read More

View Article and Full-Text PDF

A 3-month-delayed treatment with anatabine improves chronic outcomes in two different models of repetitive mild traumatic brain injury in hTau mice.

Sci Rep 2021 Apr 12;11(1):7900. Epub 2021 Apr 12.

The Roskamp Institute, 2040 Whitfield Ave., Sarasota, FL, 34243, USA.

To date, an overwhelming number of preclinical studies have addressed acute treatment in mild TBI (mTBI) and repetitive mTBI (r-mTBI), whereas, in humans, there often exists a significant time gap between the injury and the first medical intervention. Our study focused on a delayed treatment with anatabine, an anti-inflammatory compound, in hTau mice using two different models of r-mTBI. The rationale for using two models of the same impact but different frequencies (5 hit mTBI over 9 days and 24 hit mTBI over 90 days) was chosen to address the heterogeneity of r-mTBI in clinical population. Read More

View Article and Full-Text PDF

The Botrytis cinerea Crh1 transglycosylase is a cytoplasmic effector triggering plant cell death and defense response.

Nat Commun 2021 04 12;12(1):2166. Epub 2021 Apr 12.

School of Plant Sciences and Food Security, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Crh proteins catalyze crosslinking of chitin and glucan polymers in fungal cell walls. Here, we show that the BcCrh1 protein from the phytopathogenic fungus Botrytis cinerea acts as a cytoplasmic effector and elicitor of plant defense. BcCrh1 is localized in vacuoles and the endoplasmic reticulum during saprophytic growth. Read More

View Article and Full-Text PDF

A complex of distal appendage-associated kinases linked to human disease regulates ciliary trafficking and stability.

Proc Natl Acad Sci U S A 2021 Apr;118(16)

Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710

Cilia biogenesis is a complex, multistep process involving the coordination of multiple cellular trafficking pathways. Despite the importance of ciliogenesis in mediating the cellular response to cues from the microenvironment, we have only a limited understanding of the regulation of cilium assembly. We previously identified Tau tubulin kinase 2 (TTBK2) as a key regulator of ciliogenesis. Read More

View Article and Full-Text PDF

Astrogliosis and episodic memory in late life: higher GFAP is related to worse memory and white matter microstructure in healthy aging and Alzheimer's disease.

Neurobiol Aging 2021 Feb 26;103:68-77. Epub 2021 Feb 26.

Department of Neurology, University of Colorado Alzheimer's & Cognition Center, Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Astrocytes play a formative role in memory consolidation during physiological conditions; when dysregulated, astrocytes release glial fibrillary acidic protein (GFAP), which has been linked with negative memory outcomes in animal studies. We examined the association between blood GFAP, memory, and white matter (WM) integrity, accounting for blood markers of AD pathology (i.e. Read More

View Article and Full-Text PDF
February 2021

Distinctive clinical presentation and pathogenic specificities of anti-AK5 encephalitis.

Brain 2021 Apr 12. Epub 2021 Apr 12.

French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France.

Limbic encephalitis (LE) with antibodies against adenylate kinase 5 (AK5) has been difficult to characterize because of its rarity. In this study, we identified 10 new cases and reviewed 16 previously reported patients, investigating clinical features, IgG subclasses, human leukocyte antigen (HLA), and CSF proteomic profiles. Patients with anti-AK5 LE were mostly men (20/26, 76. Read More

View Article and Full-Text PDF

Heterogeneity of Cerebrospinal Fluid Biomarkers Profiles in Individuals with Distinct Levels of Cognitive Decline: A Cross-Sectional Study.

J Alzheimers Dis 2021 Apr 5. Epub 2021 Apr 5.

Laboratory of Neuroscience, Departamento e Instituto de Psiquiatria HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil.

Background: Decreased cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ), along with increased total (T-tau) and phosphorylated tau protein (P-tau), are widely accepted as core biomarkers of Alzheimer's disease (AD) pathology. Nonetheless, there are a few remaining caveats that still preclude the full incorporation of AD biomarkers into clinical practice.

Objective: To determine the frequency of clinical-biological mismatches in a clinical sample of older adults with varying degrees of cognitive impairment. Read More

View Article and Full-Text PDF

Simultaneous Detection of Six Isoforms of Tau Protein in Human Cerebrospinal Fluid by Multidimensional Mass Spectrometry-Based Targeted Proteomics.

J Proteome Res 2021 Apr 12. Epub 2021 Apr 12.

School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

Abnormal expression of Tau protein can cause the development of Alzheimer's disease (AD). So far, much evidence has demonstrated that Tau has multiple isoforms. These isoforms are suggested to have distinct physiological roles and contribute unequally to the progress of AD. Read More

View Article and Full-Text PDF

Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state.

Brain 2021 Apr 11. Epub 2021 Apr 11.

Université Paris-Saclay, CEA, CNRS, MIRCen, Laboratoire des Maladies Neurodégénératives, 92265, Fontenay-aux-Roses, France.

Deposits of different abnormal forms of tau in neurons and astrocytes represent key anatomo-pathological features of tauopathies. Although tau protein is highly enriched in neurons and poorly expressed by astrocytes, the origin of astrocytic tau is still elusive. Here, we used innovative gene transfer tools to model tauopathies in adult mouse brains and to investigate the origin of astrocytic tau. Read More

View Article and Full-Text PDF

Neurofilament Light Chain Related to Longitudinal Decline in Frontotemporal Lobar Degeneration.

Neurol Clin Pract 2021 Apr;11(2):105-116

Penn Frontotemporal Degeneration Center (JVZ, DJI, KR, L. Massimo, CTM, MG) and Department of Neurology (DJI, KR, L. Massimo, CTM, AC-P, LE, L. McCluskey, D. Wolk, MG), Department of Pathology and Laboratory Medicine and Center for Neurodegenerative Disease Research (EBL, LMS, VM-YL, JBT, JQT), Department of Psychiatry (D. Weintraub), University of Pennsylvania, Philadelphia; Institute of Neuroscience and Physiology (KB, HZ), Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory (KB, HZ), Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute at UCL (HZ); and Department of Neurodegenerative Disease (HZ), UCL Institute of Neurology, UK.

Objective: Accurate diagnosis and prognosis of frontotemporal lobar degeneration (FTLD) during life is an urgent concern in the context of emerging disease-modifying treatment trials. Few CSF markers have been validated longitudinally in patients with known pathology, and we hypothesized that CSF neurofilament light chain (NfL) would be associated with longitudinal cognitive decline in patients with known FTLD-TAR DNA binding protein ~43kD (TDP) pathology.

Methods: This case-control study evaluated CSF NfL, total tau, phosphorylated tau, and β-amyloid in patients with known FTLD-tau or FTLD-TDP pathology (n = 50) and healthy controls (n = 65) and an extended cohort of clinically diagnosed patients with likely FTLD-tau or FTLD-TDP (n = 148). Read More

View Article and Full-Text PDF

Fatty Acid-Binding Protein 3 Expression in the Brain and Skin in Human Synucleinopathies.

Front Aging Neurosci 2021 25;13:648982. Epub 2021 Mar 25.

Department of Neurology, National Hospital Organization, Sendai Nishitaga Hospital, Sendai, Japan.

Parkinson's disease (PD) and multiple system atrophy are types of adult-onset neurodegenerative disorders named synucleinopathies, which are characterized by prominent intracellular α-synuclein (αSyn) aggregates. We have previously found that αSyn aggregates and the vulnerability of dopaminergic neurons in the mouse brain are partly associated with the expression of fatty acid-binding protein 3 (FABP3, heart FABP). However, it remains to be elucidated whether FABP3 accumulation is associated with αSyn aggregates in human tissues. Read More

View Article and Full-Text PDF

Pharmacotherapy for Frontotemporal Dementia.

CNS Drugs 2021 Apr 11. Epub 2021 Apr 11.

Department of Psychiatry and Behavioral Neuroscience, Saint Louis University School of Medicine, Saint Louis, MO, USA.

Frontotemporal dementia is a heterogeneous spectrum of neurodegenerative disorders. The neuropathological inclusions are tau proteins, TAR DNA binding protein 43 kDa-TDP-43, or fused in sarcoma-ubiquitinated inclusions. Genetically, several autosomal mutations account for the heritability of the disorder. Read More

View Article and Full-Text PDF

Inhibitors of heat shock protein 70 (Hsp70) with enhanced metabolic stability reduce tau levels.

Bioorg Med Chem Lett 2021 Apr 8:128025. Epub 2021 Apr 8.

Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, 94158, United States; Institute for Neurodegenerative Disease, University of California San Francisco, San Francisco, CA, 94158, United States. Electronic address:

The molecular chaperone, Heat Shock Protein 70 (Hsp70), is an emerging drug target for neurodegenerative diseases, because of its ability to promote degradation of microtubule-associated protein tau (MAPT/tau). Recently, we reported YM-08 as a brain penetrant, allosteric Hsp70 inhibitor, which reduced tau levels. However, the benzothiazole moiety of YM-08 is vulnerable to metabolism by CYP3A4, limiting its further application as a chemical probe. Read More

View Article and Full-Text PDF

Exome sequencing revealed PDE11A as a novel candidate gene for early-onset Alzheimer's disease.

Hum Mol Genet 2021 Apr 9. Epub 2021 Apr 9.

Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China.

To identify novel risk genes and better understand the molecular pathway underlying Alzheimer's disease (ad), whole-exome sequencing (WES) was performed in 215 early-onset ad (EOAD) patients and 255 unrelated healthy controls of Han Chinese ethnicity. Subsequent validation, computational annotation and in vitro functional studies were performed to evaluate the role of candidate variants in EOAD. We identified two rare missense variants in the phosphodiesterase 11A (PDE11A) gene in individuals with EOad. Read More

View Article and Full-Text PDF

Mixed pathologies in pancreatic β cells from subjects with neurodegenerative diseases and their interaction with prion protein.

Acta Neuropathol Commun 2021 Apr 8;9(1):64. Epub 2021 Apr 8.

Neurosciences Division, Center for Applied Medical Research (CIMA), Universidad de Navarra, Pamplona, Spain.

Protein misfolding diseases refer to a variety of disorders that develop as a consequence of the misfolding of proteins in various organs. The etiologies of Parkinson's and Alzheimer's disease remain unclear, but it seems that type two diabetes and other prediabetic states could contribute to the appearance of the sporadic forms of these diseases. In addition to amylin deposition, other amyloidogenic proteins implicated in the pathophysiology of neurodegenerative diseases could have important roles in the pathogenesis of this disease. Read More

View Article and Full-Text PDF

Hsp90 co-chaperones, FKBP52 and Aha1, promote tau pathogenesis in aged wild-type mice.

Acta Neuropathol Commun 2021 Apr 8;9(1):65. Epub 2021 Apr 8.

USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, 33613, USA.

The microtubule associated protein tau is an intrinsically disordered phosphoprotein that accumulates under pathological conditions leading to formation of neurofibrillary tangles, a hallmark of Alzheimer's disease (AD). The mechanisms that initiate the accumulation of phospho-tau aggregates and filamentous deposits are largely unknown. In the past, our work and others' have shown that molecular chaperones play a crucial role in maintaining protein homeostasis and that imbalance in their levels or activity can drive tau pathogenesis. Read More

View Article and Full-Text PDF

PIKfyve activity is required for lysosomal trafficking of tau aggregates and tau seeding.

J Biol Chem 2021 Apr 5:100636. Epub 2021 Apr 5.

Neuroscience Department, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, 2340, Beerse, Belgium. Electronic address:

Tauopathies, such as Alzheimer's disease (AD), are neurodegenerative disorders characterized by the deposition of hyperphosphorylated tau aggregates. Proteopathic tau seeds spread through the brain in a temporospatial pattern, indicative of transsynaptic propagation. It is hypothesized that reducing the uptake of tau seeds and subsequent induction of tau aggregation could be a potential approach for abrogating disease progression in AD. Read More

View Article and Full-Text PDF

Tau strains shape disease.

Acta Neuropathol 2021 Apr 8. Epub 2021 Apr 8.

Center for Alzheimer's and Neurodegenerative Diseases, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Tauopathies consist of over 25 different neurodegenerative diseases that include argyrophilic grain disease (AGD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick's disease (PiD). Tauopathies are defined by brain accumulation of microtubule-associated protein tau in fibrillar aggregates, whose prevalence strongly correlates with dementia. Dominant mutations in tau cause neurodegenerative diseases, and most increase its aggregation propensity. Read More

View Article and Full-Text PDF

Alginate-Derived Mannuronate Oligosaccharide Attenuates Tauopathy through Enhancing Autophagy.

J Agric Food Chem 2021 Apr 8. Epub 2021 Apr 8.

Shenzhen Key Laboratory of Marine Bioresources and Ecology, and Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, PR China.

Polymannuronate (PM) is an acidic polysaccharide prepared from alginate, contained in edible brown seaweeds. An unsaturated mannuronate oligosaccharide (MOS) is an enzymatically depolymerized oligosaccharide prepared from PM. The effects of MOS on attenuating tauopathy were studied in HEK293/Tau cells and primary triple transgenic (3×Tg) neurons. Read More

View Article and Full-Text PDF

Age-related calcium dysregulation linked with tau pathology and impaired cognition in non-human primates.

Alzheimers Dement 2021 Apr 7. Epub 2021 Apr 7.

Departments of Neuroscience, School of Medicine, Yale University, Connecticut, USA.

Introduction: The etiology of sporadic Alzheimer's disease (AD) requires non-genetically modified animal models.

Methods: The relationship of tau phosphorylation to calcium-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) dysregulation was analyzed in aging rhesus macaque dorsolateral prefrontal cortex (dlPFC) and rat primary cortical neurons using biochemistry and immuno-electron microscopy. The influence of calcium leak from ryanodine receptors (RyRs) on neuronal firing and cognitive performance was examined in aged macaques. Read More

View Article and Full-Text PDF

Gut Microbiota Composition and Epigenetic Molecular Changes Connected to the Pathogenesis of Alzheimer's Disease.

J Mol Neurosci 2021 Apr 8. Epub 2021 Apr 8.

Department of Pharmacology, Govt. College of Pharmacy, Rohru, Himachal Pradesh, India.

Alzheimer's disease (AD) is a neurodegenerative disorder, and its pathogenesis is not fully known. Although there are several hypotheses, such as neuroinflammation, tau hyperphosphorylation, amyloid-β plaques, neurofibrillary tangles, and oxidative stress, none of them completely explain the origin and progression of AD. Emerging evidence suggests that gut microbiota and epigenetics can directly influence the pathogenesis of AD via their effects on multiple pathways, including neuroinflammation, oxidative stress, and amyloid protein. Read More

View Article and Full-Text PDF

Doxycycline Interferes With Tau Aggregation and Reduces Its Neuronal Toxicity.

Front Aging Neurosci 2021 22;13:635760. Epub 2021 Mar 22.

Instituto de Investigación en Medicina Molecular y Celular Aplicada (IMMCA) (UNT-CONICET-SIPROSA), Tucumán, Argentina.

Tauopathies are neurodegenerative disorders with increasing incidence and still without cure. The extensive time required for development and approval of novel therapeutics highlights the need for testing and repurposing known safe molecules. Since doxycycline impacts α-synuclein aggregation and toxicity, herein we tested its effect on tau. Read More

View Article and Full-Text PDF

Direct observation of the self-aggregation of R3R4 bi-repeat of Tau protein.

Chembiochem 2021 Apr 7. Epub 2021 Apr 7.

Indian Institute of Science Education Research Thiruvananthapuram, Chemistry, College of Engineering PO, 695016, Trivandrum, INDIA.

Different cryo-EM derived atomic models of in vivo tau filaments from patients with tauopathies consisted of R3 and R4 repeats of the microtubule-binding domain. In comparison, only the R3 repeat forms the core of the heparin-induced fibrils of the three repeat tau isoforms. Read More

View Article and Full-Text PDF

Synergistic Association between Plasma Aβ and p-tau in Alzheimer's Disease but Not in Parkinson's Disease or Frontotemporal Dementia.

ACS Chem Neurosci 2021 Apr 7. Epub 2021 Apr 7.

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal 405 30, Sweden.

Beta-amyloid (Aβ) triggers the phosphorylation of tau protein in Alzheimer's disease (AD), but the relationship between phosphorylated tau (p-tau) and Aβ in the blood is not elucidated. We investigated the association in individuals with AD ( = 62, including amnesic mild cognitive impairment and dementia), Parkinson's disease ( = 30), frontotemporal dementia ( = 25), and cognitively unimpaired controls ( = 41) using immunomagnetic reduction assays to measure plasma Aβ and p-tau181 concentrations. Correlation and regression analyses were performed to examine the relation between plasma levels, demographic factors, and clinical severity. Read More

View Article and Full-Text PDF

Neuroinflammation is highest in areas of disease progression in semantic dementia.

Brain 2021 Apr 6. Epub 2021 Apr 6.

Nantz National Alzheimer Center, Stanley H. Appel Department of Neurology, Houston Methodist Research Institute, Weill Cornell Medicine, Houston, TX, USA.

Despite epidemiological and genetic data linking semantic dementia to inflammation, the topography of neuroinflammation in semantic dementia, also known as the semantic variant of primary progressive aphasia, remains unclear. The pathology starts at the tip of the left temporal lobe where, in addition to cortical atrophy, a strong signal appears with the tau PET tracer 18F-flortaucipir, even though the disease is not typically associated with tau but with TDP-43 protein aggregates. Here, we characterized the topography of inflammation in semantic variant primary progressive aphasia using high-resolution PET and the tracer 11C-PBR28 as a marker of microglial activation. Read More

View Article and Full-Text PDF

Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage.

Nat Commun 2021 04 6;12(1):2076. Epub 2021 Apr 6.

Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London (UCL), London, UK.

Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. Read More

View Article and Full-Text PDF

Repetitive mild traumatic brain injury in mice triggers a slowly developing cascade of long-term and persistent behavioral deficits and pathological changes.

Acta Neuropathol Commun 2021 Apr 6;9(1):60. Epub 2021 Apr 6.

Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.

We have previously reported long-term changes in the brains of non-concussed varsity rugby players using magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and functional magnetic imaging (fMRI). Others have reported cognitive deficits in contact sport athletes that have not met the diagnostic criteria for concussion. These results suggest that repetitive mild traumatic brain injuries (rmTBIs) that are not severe enough to meet the diagnostic threshold for concussion, produce long-term consequences. Read More

View Article and Full-Text PDF

Role of Extracellular vesicles in Alzheimer's disease: Current Advances.

Authors:
Smriti Sharma

Curr Mol Med 2021 Apr 6. Epub 2021 Apr 6.

Department of Chemistry, Miranda House, University of Delhi. India.

The recent developments in the field of extracellular vesicles (EVs) point to their potential use for predicting and treating neurodegenerative diseases. This reviews focusses on the importance and latest advances in this field especially with respect to Alzheimer's disease (AD). Increasing evidence show that progression of amyloid-beta and tau brain pathology is correlated to the cognitive decline associated with AD. Read More

View Article and Full-Text PDF