Diet-derived changes in insulin metabolism in brain accelerate the development of Alzheimer's disease neuropathological features

• Autorzy: Mietelska-Porowska A. , Wieckowska A. , Dlugosz J. , Koperski M. , Wojda U.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: The western diet (WD), enriched in saturated fatty acids, cholesterol, and simple carbohydrates., is known to cause metabolic syndrome related to insulin metabolism impairment. On the other hand, metabolic syndrome is described as a potential risk factor for Alzheimer’s disease (AD). Main early AD features in brain are altered proteolysis of amyloid precursor protein (APP) and hyperphosphorylation of tau protein. AIM(S): Our aim was to verify our hypothesis that the WD causes insulin metabolism disturbances and may accelerate development of early AD hallmarks. METHOD(S): To verify this hypothesis, we compared effects of WD feeding (from 3rd month of age) in transgenic mice expressing human APP with Swedish AD-causing mutation (APPswe) compared to APPswe mice in which systemic inflammation was induced by injection of lipopolysaccharide (LPS; the model described in the abstract by J. Dlugosz), and to untreated APPswe mice. To assess AD neuropathological hallmarks, all groups were analysed at the ages of 4, 8, and 12‑months by immunohistochemical and immunoblotting analysis. RESULTS: Our results demonstrate levels of insulin resistance marker and insulin/Aβ degrading enzyme in relation to characteristic neuropathological AD hallmarks, such as occurrence, intensity of staining, and neuronal compartmentalisation of phosphorylated isoform of Tau protein, and the level of APP full-length protein and its pathologically truncated CTFs forms, in the hippocampus and cortex of mice brains. CONCLUSIONS: Obtained results indicate that WD is linked to insulin metabolism impairment and leads to accelerated over-phosphorylation of tau protein and proteolysis of APP. This suggests that the WD, via impairment in insulin metabolism, may accelerate the development of AD. FINANCIAL SUPPORT: Financed by National Science Center grant no. 2014/15/D/NZ4/04361.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2019
• Tom: 79
• Numer: Suppl.1
• Opis fizyczny: p.XLIV-XLV

Twórcy

autor

Mietelska-Porowska A.

• Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland

autor

Wieckowska A.

• Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland

autor

Dlugosz J.

• Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland

autor

Koperski M.

• Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland

autor

Wojda U.

• Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland