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The liver is the main site of ApoE synthesis and secretion, and the ApoE gene, especially the 4 allele, is the strongest genetic risk factor for sporadic AD, and some of the AD disease markers and therapeutic effects are even dependent on differences in ApoE genotype [82, 83]
Macrophages are central to this process, orchestrating immune responses via cytokine secretion, phagocytosis of pathogens, apoptotic cells, and ECM debris, and facilitating tissue remodeling by releasing proteolytic enzymes and their inhibitors (135)
