Introduction The E4 allele of the APOE gene is one of the greatest genetic risk factor of late onset AD ( The direct influence of the E4 allele on FA-related bioenergetics (i.e., the transport and use of metabolites, in this case FAs, for energy) within the cerebrovasculature requires further attention, specifically in E4 carriers because of their increased cerebrovascular vulnerability observed with age which could impair nutrient transport to the brain and affect proper neuronal and glial functioning ( APOE genotypes, despite the fact that cerebrovascular FAO has been suggested to be an essential process in maintaining its transport functions ( The L-carnitine shuttle system is indispensable to FAO given that activated long chain fatty acids (LCFAs) have to be esterified with L-carnitine to form acylcarnitines in order to enter mitochondria (Figure 1)
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Several 20242025 integrative meta-analyses also show that adding microbial metabolites (SCFAs, bile acids, LPS/LBP) and systemic inflammatory markers to microbiome-based models significantly improves diagnostic accuracy, implying that microbiome changes are informative but insufficient for high-fidelity prediction [190]
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Sep 2021;203(7):3793-3802
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