scholarly journals Tau pathology in early Alzheimer’s disease disrupts selective neurophysiological network dynamics

2019 ◽  
Author(s):  
Ece Kocagoncu ◽  
Andrew Quinn ◽  
Azadeh Firouzian ◽  
Elisa Cooper ◽  
Andrea Greve ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Information Transfer ◽  
Functional Organization ◽  
Eigenvector Centrality ◽  
Tau Pathology ◽  
Specific Effects ◽  
Graph Theoretical Approach ◽  
Early Alzheimer’S Disease ◽  
Network Disruption

AbstractThe role of aggregation of misfolded Tau protein in the pathogenesis of Alzheimer’s disease is the subject of rapid biomarker development and new therapeutic strategies to slow or prevent dementia. We tested the hypothesis that Tau pathology is associated with functional organization of widespread neurophysiological networks. We used electro-magnetoencephalography (E/MEG) in combination with [18F]AV1451 PET scanning to quantify Tau-dependent network disruption. Using a graph theoretical approach to MEG connectivity, we quantified nodal measures of functional segregation, centrality and efficiency of information transfer. We correlated these metrics against the nodes’ uptake of [18F]AV1451. There were both regional- and frequency-specific effects of Tau levels on the efficiency of information transfer and network segregation in early AD. Tau correlated with temporal regional participation coefficient (in delta, theta, beta bands); and temporal lobar eigenvector centrality (in theta, alpha, beta bands), but greater eccentricity at higher frequencies (gamma). The results support the translational development of neurophysiological “signatures” as biomarkers of Alzheimer’s disease, with potential to facilitate experimental medicines studies.

scholarly journals Tau pathology in early Alzheimer's disease is linked to selective disruptions in neurophysiological network dynamics

2020 ◽  
Vol 92 ◽  
pp. 141-152
Author(s):  
Ece Kocagoncu ◽  
Andrew Quinn ◽  
Azadeh Firouzian ◽  
Elisa Cooper ◽  
Andrea Greve ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Network Dynamics ◽  
Tau Pathology ◽  
Early Alzheimer’S Disease

scholarly journals Propagation of Tau Pathology in a Model of Early Alzheimer's Disease

Neuron ◽  
2012 ◽  
Vol 73 (4) ◽  
pp. 685-697 ◽  
Author(s):  
Alix de Calignon ◽  
Manuela Polydoro ◽  
Marc Suárez-Calvet ◽  
Christopher William ◽  
David H. Adamowicz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Pathology ◽  
Early Alzheimer’S Disease

Parahippocampal tau pathology in healthy aging, mild cognitive impairment, and early Alzheimer's disease

2002 ◽  
Vol 51 (2) ◽  
pp. 182-189 ◽  
Author(s):  
Thomas W. Mitchell ◽  
Elliott J. Mufson ◽  
Julie A. Schneider ◽  
Elizabeth J. Cochran ◽  
Jonathan Nissanov ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Healthy Aging ◽  
Tau Pathology ◽  
Early Alzheimer’S Disease

scholarly journals Astrocytic expression of the Alzheimer’s disease risk allele, ApoEε4, potentiates neuronal tau pathology in multiple preclinical models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Angela Marie Jablonski ◽  
Lee Warren ◽  
Marija Usenovic ◽  
Heather Zhou ◽  
Jonathan Sugam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Risk ◽  
In Vitro Models ◽  
Tau Pathology ◽  
Adeno Associated Virus ◽  
Human Apoe ◽  
Specific Effects ◽  
Tau Aggregation

AbstractApoEε4 is a major genetic risk factor for Alzheimer’s disease (AD), a disease hallmarked by extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). The presence of the ApoEε4 allele is associated with increased Aβ deposition and a role for ApoEε4 in the potentiation of tau pathology has recently emerged. This study focused on comparing the effects of adeno-associated virus (AAV)-mediated overexpression of the three predominant human ApoE isoforms within astrocytes. The isoform-specific effects of human ApoE were evaluated within in vitro models of tau pathology within neuron/astrocyte co-cultures, as well as in a transgenic tau mouse model. Tau aggregation, accumulation, and phosphorylation were measured to determine if the three isoforms of human ApoE had differential effects on tau. Astrocytic overexpression of the human ApoEε4 allele increased phosphorylation and misfolding of overexpressed neuronal tau in multiple models, including the aggregation and accumulation of added tau oligomers, in an isoform-specific manner. The ability of ApoEε4 to increase tau aggregation could be inhibited by an ApoEε4-specific antibody. This study indicates that astrocytic expression of ApoEε4 can potentiate tau aggregation and phosphorylation within neurons and supports a gain of toxic function hypothesis for the effect of hApoEε4 on tau.

scholarly journals Astrocytic Propagation of Tau in the Context of Alzheimer's Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Rebecca M. Fleeman ◽  
Elizabeth A. Proctor
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Significance ◽  
Glial Cells ◽  
Cell Type ◽  
Tau Pathology ◽  
Specific Effects ◽  
Signaling Mechanisms ◽  
Cell Type Specific ◽  
The Brain

More than 6 million Americans are currently living with Alzheimer's disease (AD), and the incidence is growing rapidly with our aging population. Numerous therapeutics have failed to make it to the clinic, potentially due to a focus on presumptive pathogenic proteins instead of cell-type-specific signaling mechanisms. The tau propagation hypothesis that inter-neuronal tau transfer drives AD pathology has recently garnered attention, as accumulation of pathological tau in the brain has high clinical significance in correlating with progression of cognitive AD symptoms. However, studies on tau pathology in AD are classically neuron-centric and have greatly overlooked cell-type specific effects of tau internalization, degradation, and propagation. While the contribution of microglia to tau processing and propagation is beginning to be recognized and understood, astrocytes, glial cells in the brain important for maintaining neuronal metabolic, synaptic, trophic, and immune function which can produce, internalize, degrade, and propagate tau are understudied in their ability to affect AD progression through tau pathology. Here, we showcase evidence for whether tau uptake by astrocytes may be beneficial or detrimental to neuronal health and how astrocytes and their immunometabolic functions may be key targets for future successful AD therapies.

In vivo direct relation of tau pathology with neuroinflammation in early Alzheimer’s disease

2019 ◽  
Vol 266 (9) ◽  
pp. 2186-2196 ◽  
Author(s):  
Tatsuhiro Terada ◽  
Masamichi Yokokura ◽  
Tomokazu Obi ◽  
Tomoyasu Bunai ◽  
Etsuji Yoshikawa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Direct Relation ◽  
Tau Pathology ◽  
Early Alzheimer’S Disease
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