Abstract
Brain is one of the richest organs in lipid content. Phospholipids (glycerophospholipids and sphingolipids) are important building blocks of cell membranes, which provide an optimal environment for protein interactions, trafficking and function. Because of that, alterations in their cellular levels could lead to different pathogenic processes in the brain, such as in Alzheimer’s disease (AD), the most common type of dementia among older populations. There is increasing evidence that phospholipid changes occur during pathogenic processes in AD. It is known that lipids are tightly connected with metabolism of the Amyloid Precursor Protein (APP), which produces Amyloid-beta peptide (Aβ), the main component of senile plaques, which represent the main pathological hallmark of AD. However, the mechanism(s) of the lipid-effect on Aβ metabolism and AD pathogenesis is still not completely understood. This review summarizes the current knowledge on phospholipid changes occurring during normal aging and discusses phospholipid changes in the human brain associated with different stages of AD, as well changes in the cerebrospinal fluid and blood/plasma, which are interesting potential biomarkers for AD diagnosis and disease monitoring. At the end, we have discussed future perspectives of phospholipid changes as potential biomarkers and as targets for development of novel treatment strategies against AD.
Highlights
Phospholipids are structurally and biologically important molecules, which form cellular membranes and are involved in the behavior of membrane proteins, receptors, enzymes and ion channels intracellularly or at the cell surface
Cognitively normal individuals with one or two apoE4 alleles have more sulfatides in the cerebrospinal fluid (CSF) compared to apoE3 homozygous, suggesting that apolipoprotein E (apoE) may be involved in the sulfatide loss in Alzheimer’s disease (AD) [47]
Those changes were visible in an early stage of AD, confirming that observed changes of sulfatide and ceramide levels in AD brain are connected with disturbed sphingolipid metabolism [51]
Summary
Phospholipids are structurally and biologically important molecules, which form cellular membranes and are involved in the behavior of membrane proteins, receptors, enzymes and ion channels intracellularly or at the cell surface. To differentiate between pathogenic and normal aging process, it is imperative to elucidate what changes in brain phospholipid levels occur during aging. Concentrations of most lipids in the human brain decrease after the age of 50. Phosphatidylcholine (PC) brain levels decrease very slowly with age, with less than 10% loss in the period between age 40 and age 100 [2]. 10%–20% loss of phospholipids in different brain regions was observed only in individuals between age 89 and 92 compared to 33- to. Ethanolamine plasmalogen (PPE) brain levels decrease 18% (till the age of 70) and 29%. (till the age of 100), and sphingomyelin brain levels decrease 12% and 20% in the same time period, respectively [6]. Changes in other lipid classes during aging and the role of lipids in the aging brain were recently extensively reviewed [7]
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