Insulin Resistance as a Link between Amyloid-Beta and Tau Pathologies in Alzheimer's Disease

Frontiers in Aging Neuroscience
Roger MullinsDimitrios Kapogiannis

Abstract

Current hypotheses and theories regarding the pathogenesis of Alzheimer's disease (AD) heavily implicate brain insulin resistance (IR) as a key factor. Despite the many well-validated metrics for systemic IR, the absence of biomarkers for brain-specific IR represents a translational gap that has hindered its study in living humans. In our lab, we have been working to develop biomarkers that reflect the common mechanisms of brain IR and AD that may be used to follow their engagement by experimental treatments. We present two promising biomarkers for brain IR in AD: insulin cascade mediators probed in extracellular vesicles (EVs) enriched for neuronal origin, and two-dimensional magnetic resonance spectroscopy (MRS) measures of brain glucose. As further evidence for a fundamental link between brain IR and AD, we provide a novel analysis demonstrating the close spatial correlation between brain expression of genes implicated in IR (using Allen Human Brain Atlas data) and tau and beta-amyloid pathologies. We proceed to propose the bold hypotheses that baseline differences in the metabolic reliance on glycolysis, and the expression of glucose transporters (GLUT) and insulin signaling genes determine the vulnerability of different br...Continue Reading

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Citations

Aug 20, 2019·Current Protein & Peptide Science·Luping YangRongjiang Jin
Jun 27, 2020·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Erden ErenDimitrios Kapogiannis
Aug 29, 2018·Neural Plasticity·Jenna BloemerVishnu Suppiramaniam
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Mar 27, 2020·Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring·AmanPreet Badhwar, Arsalan S Haqqani
Apr 9, 2020·Frontiers in Neuroscience·Alba M Garcia-Serrano, João M N Duarte
Jun 29, 2018·Frontiers in Neuroscience·Shreyasi Chatterjee, Amritpal Mudher
Apr 9, 2019·Journal of Alzheimer's Disease : JAD·Maja MustapicDimitrios Kapogiannis
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Sep 29, 2019·Journal of Alzheimer's Disease : JAD·Sini ToppalaJuha O Rinne
Sep 14, 2019·Current Alzheimer Research·Roger J MullinsDimitrios Kapogiannis
Aug 22, 2018·Frontiers in Aging Neuroscience·Elena D OsipovaAlla B Salmina
Sep 15, 2020·Life Sciences·Vivek Kumar Sharma, Thakur Gurjeet Singh
Feb 5, 2021·Frontiers in Neuroscience·Andreza Fabro de BemJade de Oliveira
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Jun 8, 2021·Frontiers in Neuroscience·Natalia KyrtataBen R Dickie
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Aug 6, 2021·Frontiers in Neuroscience·Zenghui WeiSandra E Reznik
Aug 28, 2021·Antioxidants·Maria Assunta PotenzaMonica Montagnani

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Methods Mentioned

BETA
blood draw
blood draws
gene array

Clinical Trials Mentioned

NCT01517100
NCT02460783
NCT01255163

Software Mentioned

MATLAB
ProFit
PRESS
MRIcroGL

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