Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline

Alzheimer’s Research & Therapy, 2022 · DOI: https://doi.org/10.1186/s13195-021-00948-8 · Published: January 4, 2022

Simple Explanation

This study investigates how fatty acids in the blood relate to cognitive decline, considering the influence of the ApoE-ε4 gene and sex. The study found that in people without the ApoE-ε4 gene and in women, higher levels of certain fats in the blood were linked to a greater chance of cognitive decline. Understanding how ApoE-ε4 and sex affect metabolism can help in creating personalized treatments for cognitive decline.

Study Duration

12-year follow-up

Participants

N=368 older subjects

Evidence Level

Not specified

Key Findings

1
Increased circulating levels of free fatty acids, acyl-carnitines and pantothenic acid were found among those participants who had greater odds of cognitive decline over a 12-year follow-up.
2
Metabolomic alterations were specific for ApoE-ɛ4 non-carriers and women.
3
ApoE-ε4 genotype was characterized by a richer lipid profile, with increased circulating content of FFAs and ACs, but only within the control subjects.

Research Summary

This study demonstrates that the early onset of CD may possibly be preceded by profound alterations in fatty acid metabolism and related metabolic pathways, which are in turn modulated by ApoE-ε4 and sex. Various circulating serum metabolites, including free fatty acids, acyl-carnitines and other energy-related metabolites, were associated with CD in an ApoE and/or sex dependent manner. The study emphasizes the need for further investigating the within-group differences triggered by inter-individual variability factors (i.e., metabotyping), which in turn would facilitate the development of more effective preventive, diagnostic and treatment approaches in the context of precision medicine.

Practical Implications

Personalized Therapies

Understanding ApoE-ε4 and sex-dependent metabolism can help develop personalized therapeutic approaches for cognitive decline.

Early Diagnosis

Identifying early alterations in fatty acid metabolism could lead to earlier diagnosis and intervention in cognitive decline.

Risk Stratification

Considering ApoE-ε4 genotype and sex can improve risk stratification for cognitive decline and Alzheimer's disease.

Study Limitations

1
Stratification of the study population may inherently limit the statistical power of the stratified analyses.
2
CD cases and controls were poorly balanced for the ApoE-ε4 status and sex, and each of the subgroups under study had different sample sizes.
3
The study design was limited to individual from the Bordeaux center of the 3C study, which might bias the results (e.g., dietary habits).

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