Immunometabolism and alzheimer's disease: alteration of microglial metabolic function with age and cerebral amyloidosis
Ana Rubio Araiz
Institute of Neuroscience of the Trinity College (Dublin, Ireland)
Microglia are multifunctional cells in charge of maintaining cerebral homeostasis and neuronal health. During ageing and neurodegeneration, microglia become dysfunctional and display altered phagocytic capacity towards weak synapses or misfolded proteins such amyloid-β (Aβ) in Alzheimer's disease (AD). Our group previously reported that microglia adopt a glycolytic phenotype when challenged with an inflammatory stimulus and that it affects their phagocytic function. Here, our objective was to assess the effect of ageing on microglial metabolic signature in cells prepared from a mouse model of AD and wild type mice.
Microglia isolated from young (3-6 months), mature (9-12 months), aged (18-20 months) and senescent (>24 months) APP/PS1 and wild type mice were maintained in culture and analysed ex vivo. Metabolic changes were evaluated using the SeaHorse Extracellular Flux Analyser. Microglial phagocytic capacity and expression of key enzymes driving glycolysis were assessed by immunocytochemistry.
We report age- and genotype- related increases in glycolysis in microglia, corroborated by modifications in expression of key glycolytic enzymes. This was accompanied by altered phagocytosis of amyloid-β.
Microglial metabolism shifts towards a glycolytic phenotype with age and this is exacerbated by cerebral amyloidosis. This compromise their metabolic efficiency and may explain the reduced phagocytic function of the cells during ageing and in AD. Therefore, rebalancing metabolic function in microglia may restore their function and open new therapeutic perspectives for AD.
Host: Jimena Baleriola