Alz Res Therapy: Gender and apolipoproteins that influence fatty acid metabolism

Cognitive decline (CD), Alzheimer's disease (AD) and other forms of dementia are major health concerns due to an aging global population

Among lipids, fatty acids are thought to play important roles in neurotransmission, neuronal membrane structure and plasticity, neuroinflammation, and many other processes

The ɛ4 allele of the lipoprotein E (ApoE) gene and female sex are strong risk factors for CD and AD

In particular, CD subjects carrying the apolipoprotein-ɛ4 allele suffer from early and acute glucose hypometabolism, which is often accompanied by enhanced fatty acid metabolism

Neu et al reported that among apolipoprotein-ɛ4 carriers, the risk of AD or mild cognitive impairment (MCI) did not differ significantly between men and women, considering a broad age window (55-85 years), but Women are at increased risk compared with men at younger ages (AD 65-75 years, MCI 55-70 years)

In this context, metabolomics shows great potential to study the profound effects of CD and dementia on metabolism and ultimately phenotype

Here, Raúl González‑Domínguez et al.

To investigate early alterations in the serum metabolome of fatty acids associated with cognitive decline, here they performed a targeted metabolomic analysis of a nested case-control study (N=368) of dementia part of a prospective population cohort

They found that when the entire study population was considered, levels of circulating free fatty acids, acylcarnitines and pantothenic acid increased in those participants with greater odds of cognitive decline at 12 years of follow-up