Comorbidity Analysis Between Alzheimer's Disease and Type 2 Diabetes Mellitus (T2DM) Based on Shared Pathways and the Role of T2DM Drugs

Overview

Journal J Alzheimers Dis

Publisher Sage Publications

Specialties Geriatrics
Neurology

Date 2017 Sep 19

PMID 28922161

Citations 35

Authors

Reagon Karki

Alpha Tom Kodamullil

Martin Hofmann-Apitius

Affiliations

Soon will be listed here.

Abstract

Background: Various studies suggest a comorbid association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) indicating that there could be shared underlying pathophysiological mechanisms.

Objective: This study aims to systematically model relevant knowledge at the molecular level to find a mechanistic rationale explaining the existing comorbid association between AD and T2DM.

Method: We have used a knowledge-based modeling approach to build two network models for AD and T2DM using Biological Expression Language (BEL), which is capable of capturing and representing causal and correlative relationships at both molecular and clinical levels from various knowledge resources.

Results: Using comparative analysis, we have identified several putative "shared pathways". We demonstrate, at a mechanistic level, how the insulin signaling pathway is related to other significant AD pathways such as the neurotrophin signaling pathway, PI3K/AKT signaling, MTOR signaling, and MAPK signaling and how these pathways do cross-talk with each other both in AD and T2DM. In addition, we present a mechanistic hypothesis that explains both favorable and adverse effects of the anti-diabetic drug metformin in AD.

Conclusion: The two computable models introduced here provide a powerful framework to identify plausible mechanistic links shared between AD and T2DM and thereby identify targeted pathways for new therapeutics. Our approach can also be used to provide mechanistic answers to the question of why some T2DM treatments seem to increase the risk of AD.

Citing Articles

Effects of the therapeutic correction of U1 snRNP complex on Alzheimer's disease.

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Identification of the Shared Gene Signatures Between Alzheimer's Disease and Diabetes-Associated Cognitive Dysfunction by Bioinformatics Analysis Combined with Biological Experiment.

Chen Y, Ji X, Bao Z J Alzheimers Dis. 2024; 101(2):611-625.

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Effects of chronic treatment with metformin on brain glucose hypometabolism and central insulin actions in transgenic mice with tauopathy.

Hurtado-Carneiro V, LeBaut-Ayuso Y, Velazquez E, Flores-Lamas C, Fernandez-de la Rosa R, Garcia-Garcia L Heliyon. 2024; 10(15):e35752.

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Local patterns of genetic sharing challenge the boundaries between neuropsychiatric and insulin resistance-related conditions.

Fanelli G, Franke B, Fabbri C, Werme J, Erdogan I, De Witte W medRxiv. 2024; .

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Comorbidity Genes of Alzheimer's Disease and Type 2 Diabetes Associated with Memory and Cognitive Function.

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PMID: 38396891 PMC: 10889845. DOI: 10.3390/ijms25042211.

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