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. 2022 Aug 8:14:981868.
doi: 10.3389/fnagi.2022.981868. eCollection 2022.

Serine ether glycerophospholipids: Decrements in the frontal cortex associated with mild cognitive impairment and Alzheimer's disease

Paul L Wood  1 , Randall L Woltjer  2
Affiliations

Serine ether glycerophospholipids: Decrements in the frontal cortex associated with mild cognitive impairment and Alzheimer's disease

Paul L Wood et al. Front Aging Neurosci. .

Abstract

Ether glycerophospholipids (GPL) are involved in membrane fluidity and fusion. Vinyl-ether GPL are also conjectured to provide antioxidant capacity in the brain. The roles of these lipids in the processes involved in the development of dementia are not understood but choline and ethanolamine vinyl-ether GPL (i.e., plasmalogens) are decreased in the brains of subjects with dementia. In contrast, serine ether and vinyl-ether GPL have not been investigated in human brain. We therefore undertook an evaluation of these lipids, utilizing high-resolution mass spectrometry (HR-MS), in tissues from control and dementia subjects that we had previously characterized in-depth. We can report for the first time that a number of serine ether GPL and a more limited number of serine plasmalogens are present in human frontal cortex. In addition, we found that some of these frontal cortex lipids are decreased in Mild Cognitive Impairment (MCI), early-onset Alzheimer's disease (EOAD), and late-onset AD (LOAD). In contrast no alterations in serine ether GPL were monitored in the frontal cortex of donors with schizophrenia, demonstrating disease specificity. These data suggest that further studies of the roles of ether GPL, including serine ether GPL, in brain function are worthy of undertaking.

Keywords: Alzheimer’s; MCI; dementia; frontal cortex; serine ether glycerophospholipid.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Structure of PSe 36:1 (e18:0/18:1). The glycerol backbone possesses phosphoserine as the polar headgroup at sn-3, oleic acid via an acyl bond at sn-2, and stearyl alcohol via an alkyl bond (i.e., ether) at sn-1. In the case of a plasmalogen the bond at sn-1 would be an alkenyl bond (i.e., a double bond between the first 2 carbons after the -O-CH2.
FIGURE 2
FIGURE 2
(A) Relative levels of ether (PSe) serine GPL in the frontal cortex gray matter (GM) in controls (black bar), Mild Cognitive Impairment (MCI; red bars), early onset dementia (EOAD; blue bars) and late-onset dementia (LOAD; green bars). *p < 0.01; **p < 0.05. Relative levels are the ratio of the peak intensity of each serine lipid to that of the peak intensity of phosphatidylcholine 34:2 [phosphatidylcholine (PC) 34:2] multiplied by 100 to yield a percentage (Mean ± SEM). (B) Relative levels of ether (PSe) and vinyl-ether (PSp) serine GPL in the frontal cortex white matter (GM) in controls (black bar), Mild Cognitive Impairment (MCI; red bars), early onset dementia (EOAD; blue bars) and late-onset dementia (LOAD; green bars). *p < 0.01. Relative levels are the ratio of the peak intensity of each serine lipid to that of the peak intensity of phosphatidylcholine 34:2 (PC 34:2) multiplied by 100 to yield a percentage (Mean ± SEM).
FIGURE 3
FIGURE 3
Relative levels of ether (PSe) serine GPL in the frontal cortex white matter (WM) in controls (white bar) and subjects with a history of schizophrenia (gray bars). Relative levels are the ratio of the peak intensity of each serine lipid to that of the peak intensity of phosphatidylcholine 34:2 (PC 34:2) multiplied by 100 to yield a percentage (Mean ± SEM).
FIGURE 4
FIGURE 4
Relative levels of ether (PSe) serine GPL in the frontal cortex gray matter (GM) in controls (white bar) and subjects with a history of schizophrenia (gray bars). Relative levels are the ratio of the peak intensity of each serine lipid to that of the peak intensity of phosphatidylcholine 34:2 (PC 34:2) multiplied by 100 to yield a percentage (Mean ± SEM).
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