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Acknowledgements Illustrations were created with Abbreviations APOE Apolipoprotein E AD Alzheimers disease FAD Familial Alzheimers disease MCI Mild cognitive impairment APP Amyloid precursor protein PSEN1 Presenilin 1 PSEN2 Presenilin 2 A Amyloid beta NFT Neurofibrillary tangles ABC ATP-binding cassette ABCA1 ATP-binding cassette transporter 1 ABCG1 ATP-binding cassette subfamily G member 1 LDLR Low-density lipoprotein receptor VLDLR Very low-density lipoprotein receptor LRP1 Low-density lipoprotein receptor-related protein 1 APOER2 Apolipoprotein E receptor 2 HSPGs Heparan sulfate proteoglycans TREM2 Triggering receptor expressed on myeloid cells 2 CNS Central nervous system BBB Blood-brain-barrier iPSC Induced pluripotent stem cell DAM Disease associated microglia AAV Adeno-associated virus Author contributions AAB reviewed the literature, wrote the manuscript and prepared the figures

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AMPK phosphorylates NRF2 at the Ser550 residue located in the canonical NES sequence, facilitating NRF2 nuclear accumulation, probably by inhibiting nuclear export [212], and this effect is enhanced by GSK-3 inhibition [213]