WESTERN DIET – FROM MICROGLIA DYSFUNCTION TO THE ACCELERATION OF ALZHEIMER'S DISEASE PATHOLOGY

• Published in: Acta neurobiologiae experimentalis Vol. 82; p. XLIX
• Main Authors: Więckowska‑Gacek, Angelika, Mietelska‑Porowska, Anna, Domańska, Justyna, Wojda, Urszula
• Format: Journal Article
• Language: English
• Published: Warsaw Polish Academy of Sciences 01-01-2022
• Subjects: Alzheimer's disease; Carbohydrates; Cholesterol; Cytoskeleton; Destabilization; Diet; Fatty acids; Inflammation; Microglia; Mutation; Neurodegenerative diseases; Pathology; Peptides; Phagocytes; Phagocytosis; Phosphorylation; Proteins; Risk analysis; Risk factors; Senile plaques; Tau protein; Transgenic mice
• ISSN: 0065-1400; 1689-0035

Microglial phagocytosis in the early stage of Alzheimer's disease (AD) plays a beneficial role, however, during disease progression, seems to become insufficient and detrimental, and combined with their pro-inflammatory activity, directly and indirectly impact the main hallmarks of AD in the brain (amyloid‑β peptides (Aβ), and tau protein hyperphosphorylation (pTau)). We verified the hypothesis that Western diet (WD) feeding characterized by high level of simple carbohydrates, saturated fatty acids and cholesterol, accelerates microglia dysfunction, what results in deposition of Aβ, tau protein hyperphosphorylation and destabilization of neuronal cytoskeleton. Transgenic mice expressing human APP with Swedish mutation (APPswe) were divided into three age groups. 4- and 8-month-old groups represent early pre-symptomatic stages of AD, while 12-month-old animals represent later stages of AD with visible amyloid pathology. The APPswe mice were fed with WD from 3rd month of age. WD feeding accelerated activation of microglia and its M1 pro-inflammatory polarization profile, and induced dysfunction of microglia phagocytic function (↑Iba1, ↓CD68) in 8-months old mice, what resulted in enhanced production of Aβ plaques and destabilization of neurons in 12-months old mice. These results indicate that the westernized pattern of nourishment is an important modifiable risk factor of AD development.