Effect of astaxanthin in type-2 diabetes -induced APPxhQC transgenic and NTG mice

Area of Science:

• Neuroscience
• Metabolic Disorders
• Pharmacology

Background:

• Alzheimer's disease (AD) is linked to amyloid beta (Aβ) and tau protein misfolding.
• Metabolic dysfunctions, including type 2 diabetes (T2D), are increasingly associated with AD pathogenesis.
• Glutaminyl cyclase activity and pyroglutamylation are implicated in AD development.

Purpose of the Study:

• To investigate the combined impact of T2D and pyroglutamylation on AD pathology.
• To evaluate the efficacy of astaxanthin (ASX) in ameliorating AD and T2D-related pathophysiological changes.
• To explore the effects of genotype, T2D induction, and ASX treatment on cognitive function and metabolic markers.

Main Methods:

• Utilized transgenic AD mice (APPxhQC) and non-transgenic (NTG) littermates.
• Induced T2D using a high-fat diet and streptozotocin.
• Administered astaxanthin (ASX) and assessed outcomes via biochemical assays, immunofluorescence, and behavioral tests (Morris water maze).

Main Results:

• T2D exacerbated AD pathology, increasing Aβ deposition in APPxhQC mice.
• ASX treatment reversed T2D-induced memory deficits in NTG mice.
• ASX reduced Aβ levels in T2D-induced APPxhQC mice but showed limited efficacy in fully reversing AD pathology.

Conclusions:

• T2D poses an additional risk for AD pathology, characterized by increased Aβ deposition.
• ASX demonstrates potential in mitigating T2D-induced cognitive decline and reducing Aβ burden.
• ASX monotherapy may not be sufficient for managing AD in the presence of T2D comorbidity.