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Toxic Advanced Glycation End-Products-Dependent Alzheimer's Disease- Like Alternation in the Microtubule System

Hayahide Ooi1, Yoshiki Koriyama1

  • 1Graduate School and Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki, Suzuka 513-8670, Japan.

Current Alzheimer Research
|February 15, 2024
PubMed

Insights

Type 2 diabetes (T2DM) accelerates Alzheimer's Disease (AD) progression. Glyceraldehyde-derived toxic advanced glycation end-products (TAGE) from T2DM cause neuronal damage and tau pathology, linking diabetes to AD.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Pathology

Background:

  • Type 2 diabetes mellitus (T2DM) is a known risk factor for Alzheimer's Disease (AD).
  • The precise mechanisms linking T2DM to AD pathogenesis are not fully understood.
  • Advanced glycation end-products (AGEs) accumulate in diabetes and may play a role in neurodegeneration.

Purpose of the Study:

  • To explore the role of Glyceraldehyde (GA)-derived Toxic Advanced Glycation End-products (TAGE) in T2DM-associated Alzheimer's Disease.
  • To investigate the cellular and molecular mechanisms by which TAGE may contribute to AD pathology.

Main Methods:

  • Previous studies demonstrated TAGE cytotoxicity to neurons.
  • Investigation into GA-induced neurite outgrowth dysfunction.
  • Analysis of TAGE-dependent β-tubulin aggregation and tau phosphorylation.

Main Results:

  • Glyceraldehyde (GA) exposure leads to the formation of Toxic AGEs (TAGE).
  • TAGE exhibit cytotoxicity towards neurons, inducing alterations similar to those seen in AD.
  • GA induces abnormal neurite outgrowth by promoting TAGE-β-tubulin aggregation, leading to abnormal β-tubulin aggregation and tau phosphorylation.

Conclusions:

  • T2DM significantly increases the risk and progression of Alzheimer's Disease.
  • TAGE are key mediators in T2DM-related neurodegeneration and AD pathology.
  • Targeting TAGE formation or its downstream effects may offer therapeutic strategies for comorbid T2DM and AD.
Keywords:
Alzheimer’s diseaseToxic advanced glycation end-productsdiabetes mellitusglyceraldehydetau phosphorylation.β-tubulin

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