Soluble 4R0N Tau Abrogates Endocytic Vesicular Dynamics.

Abstract:

:Aggregated tau is a hallmark neuropathological feature in numerous neurodegenerative disorders. Previous studies aiming to validate aggregated tau pathology as a pathogenic driver of neurodegeneration in correlation to characteristic behavioral phenotypes have had shortcomings. Although studies on soluble tau pathology have effectively addressed these shortcomings, the role of soluble tau in the molecular pathogenesis of neurodegeneration is not yet unequivocally established. In sporadic Alzheimer's disease (AD), the relevance of soluble tau pathology in endolysosomal dysfunction and autophagic stress, some of the earliest disease manifestations, is unclear. In this study, we report that soluble 4R0N tau overexpression affects the expression levels of certain markers associated with the endolysosomal system and autophagy. Moreover, through live-cell imaging, we found that the vesicular dynamics of early endosomes were affected with respect to spatiotemporal parameters and vesicle maturation. Additionally, we observed the localization of amyloid precursor protein (APP) along the endocytic pathway and found that upon overexpression of soluble 4R0N tau, APP was preferentially localized to the endocytic compartments implicated in the amyloidogenic pathway. Overall, our observations indicate that soluble 4R0N tau abrogates the dynamics of the endolysosomal system, autophagy, and affects the trafficking of APP. Since the amyloidogenic processing of APP occurs during its progression through the endocytic pathway, our results suggest that the generation of amyloid-β (Aβ) might also be modulated.

journal_name

Front Aging Neurosci

authors

Mahendran TS,Suresh SN,Garimella L,Manjithaya R

doi

10.3389/fnagi.2020.537712

subject

Has Abstract

pub_date

2020-11-05 00:00:00

pages

537712

issn

1663-4365

journal_volume

12

pub_type

杂志文章
  • Variations in brain DNA.

    abstract::It is assumed that DNA sequences are conserved in the diverse cell types present in a multicellular organism like the human being. Thus, in order to compare the sequences in the genome of DNA from different individuals, nucleic acid is commonly isolated from a single tissue. In this regard, blood cells are widely used...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnagi.2014.00323

    authors: Avila J,Gómez-Ramos A,Soriano E

    更新日期:2014-11-25 00:00:00

  • Neurodegeneration and the Circadian Clock.

    abstract::Despite varied etiologies and symptoms, several neurodegenerative diseases-specifically, Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HDs)-share the common feature of abnormal circadian rhythms, such as those in behavior (e.g., disrupted sleep/wake cycles), physiological processes (e.g., diminished h...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnagi.2017.00170

    authors: Hood S,Amir S

    更新日期:2017-05-30 00:00:00

  • Bayesian Optimization for Neuroimaging Pre-processing in Brain Age Classification and Prediction.

    abstract::Neuroimaging-based age prediction using machine learning is proposed as a biomarker of brain aging, relating to cognitive performance, health outcomes and progression of neurodegenerative disease. However, even leading age-prediction algorithms contain measurement error, motivating efforts to improve experimental pipe...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2018.00028

    authors: Lancaster J,Lorenz R,Leech R,Cole JH

    更新日期:2018-02-12 00:00:00

  • Mindfulness-Based Intervention for People With Dementia and Their Partners: Results of a Mixed-Methods Study.

    abstract:Objective:Studies have shown preliminary support for mindfulness-based interventions benefitting people with dementia and their caregivers. However, most studies focus on these two groups separately. This study examined whether it would be possible and beneficial for people with dementia and their caregiver to jointly ...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2019.00092

    authors: Berk L,Warmenhoven F,Stiekema APM,van Oorsouw K,van Os J,de Vugt M,van Boxtel M

    更新日期:2019-04-24 00:00:00

  • Terra incognita-cerebellar contributions to neuropsychiatric and cognitive dysfunction in behavioral variant frontotemporal dementia.

    abstract::Although converging evidence has positioned the human cerebellum as an important relay for intact cognitive and neuropsychiatric processing, changes in this large structure remain mostly overlooked in behavioral variant frontotemporal dementia (bvFTD), a disease which is characterized by cognitive and neuropsychiatric...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2015.00121

    authors: Tan RH,Devenney E,Kiernan MC,Halliday GM,Hodges JR,Hornberger M

    更新日期:2015-07-02 00:00:00

  • Assessment of Age-Related Morphometric Changes of Subcortical Structures in Healthy People Using Ultra-High Field 7 Tesla Magnetic Resonance Imaging.

    abstract::Objective: To assess the age-related morphometric changes of subcortical structures in healthy people. Materials and Methods: Ultra-high field 7 tesla magnetic resonance (MR) imaging in humans was used to visualize the subcortical structures of healthy young, middle-aged and elderly participants. Using the magnetizati...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2016.00224

    authors: Wang XY,Zhao L,Yu T,Qiao L,Ni DY,Zhang GJ,Li YJ

    更新日期:2016-09-26 00:00:00

  • Gray Matter Alterations in Parkinson's Disease With Rapid Eye Movement Sleep Behavior Disorder: A Meta-Analysis of Voxel-Based Morphometry Studies.

    abstract::Background: Gray matter (GM) alterations in Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD) have been demonstrated in many neuroimaging studies using voxel-based morphometry (VBM). However, the inconsistent findings between studies cannot be applied to clinical practice as a neu...

    journal_title:Frontiers in aging neuroscience

    pub_type:

    doi:10.3389/fnagi.2020.00213

    authors: Yang C,Chang J,Liang X,Bao X,Wang R

    更新日期:2020-08-12 00:00:00

  • Pathological Changes in Microvascular Morphology, Density, Size and Responses Following Comorbid Cerebral Injury.

    abstract::Aberrations in brain microcirculation and the associated increase in blood-brain-barrier (BBB) permeability in addition to neuroinflammation and Aβ deposition observed in Alzheimer's disease (AD) and ischemia have gained considerable attention recently. However, the role of microvascular homeostasis as a pathogenic su...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2019.00047

    authors: Amtul Z,Yang J,Lee TY,Cechetto DF

    更新日期:2019-03-27 00:00:00

  • Motor Variability during Sustained Contractions Increases with Cognitive Demand in Older Adults.

    abstract::To expose cortical involvement in age-related changes in motor performance, we compared steadiness (force fluctuations) and fatigability of submaximal isometric contractions with the ankle dorsiflexor muscles in older and young adults and with varying levels of cognitive demand imposed. Sixteen young (20.4 ± 2.1 year:...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2014.00097

    authors: Vanden Noven ML,Pereira HM,Yoon T,Stevens AA,Nielson KA,Hunter SK

    更新日期:2014-05-22 00:00:00

  • Progranulin Mutations Affects Brain Oscillatory Activity in Fronto-Temporal Dementia.

    abstract:BACKGROUND:Mild cognitive impairment (MCI) is a clinical stage indicating a prodromal phase of dementia. This practical concept could be used also for fronto-temporal dementia (FTD). Progranulin (PGRN) has been recently recognized as a useful diagnostic biomarker for fronto-temporal lobe degeneration (FTLD) due to GRN ...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2016.00035

    authors: Moretti DV,Benussi L,Fostinelli S,Ciani M,Binetti G,Ghidoni R

    更新日期:2016-02-29 00:00:00

  • Mechanisms of Aβ Clearance and Degradation by Glial Cells.

    abstract::Glial cells have a variety of functions in the brain, ranging from immune defense against external and endogenous hazardous stimuli, regulation of synaptic formation, calcium homeostasis, and metabolic support for neurons. Their dysregulation can contribute to the development of neurodegenerative disorders, including ...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnagi.2016.00160

    authors: Ries M,Sastre M

    更新日期:2016-07-05 00:00:00

  • Disrupted Nodal and Hub Organization Account for Brain Network Abnormalities in Parkinson's Disease.

    abstract::The recent application of graph theory to brain networks promises to shed light on complex diseases such as Parkinson's disease (PD). This study aimed to investigate functional changes in sensorimotor and cognitive networks in Parkinsonian patients, with a focus on inter- and intra-connectivity organization in the dis...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2016.00259

    authors: Koshimori Y,Cho SS,Criaud M,Christopher L,Jacobs M,Ghadery C,Coakeley S,Harris M,Mizrahi R,Hamani C,Lang AE,Houle S,Strafella AP

    更新日期:2016-11-10 00:00:00

  • Plasma Neurofilament Light Chain May Be a Biomarker for the Inverse Association Between Cancers and Neurodegenerative Diseases.

    abstract::An inverse association may exist between cancers and neurodegenerative diseases, although convenient biomarkers for verifying this inverse association are lacking. Plasma neurofilament light chain (NfL) is a novel biomarker for neurodegenerative diseases, such as Alzheimer's disease (AD), but it has not been measured ...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2020.00010

    authors: Liu S,Huang Z,Zhang L,Pan J,Lei Q,Meng Y,Li Z

    更新日期:2020-01-29 00:00:00

  • Long-Term Dietary Folate Deficiency Accelerates Progressive Hearing Loss on CBA/Ca Mice.

    abstract::Dietary folic acid deficiency induced early hearing loss in C57BL/6J mice after 2-months, corroborates the epidemiological association previously described between vitamin deficiency and this sensory impairment. However, this strain is prone to early hearing loss, and hence we decided to analyze whether the effects ex...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2016.00209

    authors: Martínez-Vega R,Murillo-Cuesta S,Partearroyo T,Varela-Moreiras G,Varela-Nieto I,Pajares MA

    更新日期:2016-08-31 00:00:00

  • Voxel-Based Morphometry Reveals a Correlation Between Bone Mineral Density Loss and Reduced Cortical Gray Matter Volume in Alzheimer's Disease.

    abstract::Background: Decreased bone mineral density (BMD) was associated with poorer cognitive function and increased risk of Alzheimer's disease (AD). However, objective evidence for the relationship between osteoporosis and AD in humans has not been extensively described. Objectives: We aimed to evaluate the relationships be...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2020.00178

    authors: Takano Y,Tatewaki Y,Mutoh T,Morota N,Matsudaira I,Thyreau B,Nagasaka T,Odagiri H,Yamamoto S,Arai H,Taki Y

    更新日期:2020-06-17 00:00:00

  • Structure activity relationship of phenolic acid inhibitors of α-synuclein fibril formation and toxicity.

    abstract::The aggregation of α-synuclein (α-syn) is considered the key pathogenic event in many neurological disorders such as Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy, giving rise to a whole category of neurodegenerative diseases known as synucleinopathies. Although the molecular basis of...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2014.00197

    authors: Ardah MT,Paleologou KE,Lv G,Abul Khair SB,Kazim AS,Minhas ST,Al-Tel TH,Al-Hayani AA,Haque ME,Eliezer D,El-Agnaf OM

    更新日期:2014-08-05 00:00:00

  • Detrending Changes the Temporal Dynamics of a Semantic Fluency Task.

    abstract::Objective: To study the dynamics of clustering semantic fluency responses and switching between clusters. Methods: We conducted a cross-sectional study of participants (N = 60) in a study of patient reported outcomes who were given the Saint Louis University Mental Status test. Sixty-second animal naming tests were sc...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2016.00252

    authors: Lenio S,Lissemore FM,Sajatovic M,Smyth KA,Tatsuoka C,Woyczynski WA,Lerner AJ

    更新日期:2016-10-25 00:00:00

  • Altered Directed Functional Connectivity of the Hippocampus in Mild Cognitive Impairment and Alzheimer's Disease: A Resting-State fMRI Study.

    abstract::The hippocampus is generally reported as one of the regions most impacted by Alzheimer's disease (AD) and is closely associated with memory function and orientation. Undirected functional connectivity (FC) alterations occur in patients with mild cognitive impairment (MCI) and AD, and these alterations have been the su...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2019.00326

    authors: Xue J,Guo H,Gao Y,Wang X,Cui H,Chen Z,Wang B,Xiang J

    更新日期:2019-12-03 00:00:00

  • Cognitively Engaging Activity Is Associated with Greater Cortical and Subcortical Volumes.

    abstract::As the population ages and dementia becomes a growing healthcare concern, it is increasingly important to identify targets for intervention to delay or attenuate cognitive decline. Research has shown that the most successful interventions aim at altering lifestyle factors. Thus, this study examined how involvement in ...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2016.00094

    authors: Seider TR,Fieo RA,O'Shea A,Porges EC,Woods AJ,Cohen RA

    更新日期:2016-05-02 00:00:00

  • Herpes simplex virus type 1 and Alzheimer's disease: increasing evidence for a major role of the virus.

    abstract::Herpes simplex virus type 1 (HSV1), when present in brain of carriers of the type 4 allele of the apolipoprotein E gene (APOE), has been implicated as a major factor in Alzheimer's disease (AD). It is proposed that virus is normally latent in many elderly brains but reactivates periodically (as in the peripheral nervo...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnagi.2014.00202

    authors: Itzhaki RF

    更新日期:2014-08-11 00:00:00

  • Pathways to decoding the clinical potential of stress response FOXO-interaction networks for Huntington's disease: of gene prioritization and context dependence.

    abstract::The FOXO family of transcription factors is central to the regulation of organismal longevity and cellular survival. Several studies have indicated that FOXO factors lie at the center of a complex network of upstream pathways, cofactors and downstream targets (FOXO-interaction networks), which may have developmental a...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2013.00022

    authors: Parmentier F,Lejeune FX,Neri C

    更新日期:2013-06-13 00:00:00

  • Key Aging-Associated Alterations in Primary Microglia Response to Beta-Amyloid Stimulation.

    abstract::Alzheimer's disease (AD) is characterized by a progressive cognitive decline and believed to be driven by the self-aggregation of amyloid-β (Aβ) peptide into oligomers and fibrils that accumulate as senile plaques. It is widely accepted that microglia-mediated inflammation is a significant contributor to disease patho...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2017.00277

    authors: Caldeira C,Cunha C,Vaz AR,Falcão AS,Barateiro A,Seixas E,Fernandes A,Brites D

    更新日期:2017-08-31 00:00:00

  • Development and evaluation of a self-administered on-line test of memory and attention for middle-aged and older adults.

    abstract::There is a need for rapid and reliable Internet-based screening tools for cognitive assessment in middle-aged and older adults. We report the psychometric properties of an on-line tool designed to screen for cognitive deficits that require further investigation. The tool is composed of measures of memory and executive...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2014.00335

    authors: Troyer AK,Rowe G,Murphy KJ,Levine B,Leach L,Hasher L

    更新日期:2014-12-10 00:00:00

  • Smart Aging Platform for Evaluating Cognitive Functions in Aging: A Comparison with the MoCA in a Normal Population.

    abstract::Background: Smart Aging is a Serious games (SGs) platform in a 3D virtual environment in which users perform a set of screening tests that address various cognitive skills. The tests are structured as 5 tasks of activities of daily life in a familiar environment. The main goal of the present study is to compare a cogn...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2017.00379

    authors: Bottiroli S,Tassorelli C,Lamonica M,Zucchella C,Cavallini E,Bernini S,Sinforiani E,Pazzi S,Cristiani P,Vecchi T,Tost D,Sandrini G

    更新日期:2017-11-21 00:00:00

  • Graph analysis of verbal fluency test discriminate between patients with Alzheimer's disease, mild cognitive impairment and normal elderly controls.

    abstract::Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the ...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2014.00185

    authors: Bertola L,Mota NB,Copelli M,Rivero T,Diniz BS,Romano-Silva MA,Ribeiro S,Malloy-Diniz LF

    更新日期:2014-07-29 00:00:00

  • Characterizing spatial tuning functions of neurons in the auditory cortex of young and aged monkeys: a new perspective on old data.

    abstract::Age-related hearing deficits are a leading cause of disability among the aged. While some forms of hearing deficits are peripheral in origin, others are centrally mediated. One such deficit is the ability to localize sounds, a critical component for segregating different acoustic objects and events, which is dependent...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2012.00036

    authors: Engle JR,Recanzone GH

    更新日期:2013-01-04 00:00:00

  • The Role of Microglia in Prion Diseases: A Paradigm of Functional Diversity.

    abstract::Inflammation is a major component of neurodegenerative diseases. Microglia are the innate immune cells in the central nervous system (CNS). In the healthy brain, microglia contribute to tissue homeostasis and regulation of synaptic plasticity. Under disease conditions, they play a key role in the development and maint...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnagi.2017.00207

    authors: Obst J,Simon E,Mancuso R,Gomez-Nicola D

    更新日期:2017-06-23 00:00:00

  • Protein-Protein Interactions in Alpha-Synuclein Biogenesis: New Potential Targets in Parkinson's Disease.

    abstract::Parkinson's disease (PD) is a debilitating neurodegenerative disorder defined by a loss of dopamine-producing neurons in the substantia nigra in the brain. It is associated with cytosolic inclusions known as Lewy bodies. The major component of Lewy bodies is aggregated alpha-synuclein. The molecular mechanism of alpha...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2020.00072

    authors: Hernandez SM,Tikhonova EB,Karamyshev AL

    更新日期:2020-03-17 00:00:00

  • The McGill Transgenic Rat Model of Alzheimer's Disease Displays Cognitive and Motor Impairments, Changes in Anxiety and Social Behavior, and Altered Circadian Activity.

    abstract::The McGill-R-Thy1-APP transgenic rat is an animal model of the familial form of Alzheimer's disease (AD). This model mirrors several neuropathological hallmarks of the disease, including the accumulation of beta-amyloid and the formation of amyloid plaques (in homozygous animals only), neuroinflammation and the gradua...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2018.00250

    authors: Petrasek T,Vojtechova I,Lobellova V,Popelikova A,Janikova M,Brozka H,Houdek P,Sladek M,Sumova A,Kristofikova Z,Vales K,Stuchlík A

    更新日期:2018-08-28 00:00:00

  • Cognitive Variability during Middle-Age: Possible Association with Neurodegeneration and Cognitive Reserve.

    abstract::Objective: Increased variability in cognition with age has been argued as an indication of pathological processes. Focusing on early detection of neurodegenerative disorders, we investigated variability in cognition in healthy middle-aged adults. In order to understand possible determinants of this variability, we als...

    journal_title:Frontiers in aging neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnagi.2017.00188

    authors: Ferreira D,Machado A,Molina Y,Nieto A,Correia R,Westman E,Barroso J

    更新日期:2017-06-09 00:00:00