Plasmalogen Deficit: A New and Testable Hypothesis for the Etiology of Alzheimer’s Disease

Wood, Paul L.; Khan, M Amin; Mankidy, Rishikesh; Smith, Tara; Goodenowe, Dayan B.

doi:10.5772/17630

Cited by 6 publications

(8 citation statements)

References 71 publications

(88 reference statements)

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“…The cell membrane phospholipid composition affects the protein composition and activity of the cell. We have previously shown that increasing membrane levels of 22:6n-3 EtnPls increases the levels of cholesterol esterifying enzymes [19] and non-amyloidogenic amyloid precursor processing enzymes [33]. Recently, it has been shown that 22:6n-3 supplementation increases the membrane 22:6n-3 levels in rats and that this increase resulted in a decreased incidence of experimentally induced BC [34].…”

Section: Discussionmentioning

confidence: 97%

Plasmalogen Deficiency and Overactive Fatty Acid Elongation Biomarkers in Serum of Breast Cancer Patients Pre- and Post-Surgery—New Insights on Diagnosis, Risk Assessment, and Disease Mechanisms

Tomida

Goodenowe²,

Koyama

et al. 2021

Cancers

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The polyunsaturated fatty acid (PUFA) elongase, ELOVL5, is upregulated in breast cancer (BC) vs. adjacent normal tissue. We performed a comprehensive lipid metabolomic analysis of serum using high-resolution accurate mass spectrometry from two case-control studies that included non-BC, BC subjects pre-surgery, and BC subjects one-month post-surgery to determine if the metabolic signatures of over-active fatty acid elongation and other lipid changes could be detected in BC vs. non-BC subjects: study 1 (n = 48: non-BC, n = 69: pre-surgery BC); study 2 (blinded validation: n = 121: non-BC, n = 62: pre-surgery BC, n = 31: one month post-surgery). The ratio of the ELOVL5 precursor, linoleic acid (18:2) to a non-ELOVL5 precursor, oleic acid (18:1) was evaluated in multiple lipid pools (phosphatidylethanolamine (PtdEtn), phosphatidylcholine (PtdCho), lyso-PtdCho, and free fatty acids). This ratio was lower in pre-surgery BC subjects in all pools in both studies (p < 0.001). At one-month post-surgery, the 18:2/18:1 ratios increased vs. pre-surgery and were no longer different from non-BC subjects (p > 0.05 expect for lyso-PtdCho). In contrast to the elongation biomarkers, docosahexaenoic acid (22:6n-3) containing ethanolamine plasmalogen (EtnPls) species were observed to be further decreased in BC subjects one-month post-surgery vs. pre-surgery levels (p < 0.001). These results are consistent with the hypothesis that ELOVL5 is upregulated in BC tissue, which would result in the selective depletion of 18:2 vs. 18:1 containing lipid species. Surgical removal of the tumor removes the overactive ELOVL5 effect on serum lipids. In contrast, the low EtnPls levels do not appear to be caused by BC tumor activity and may be pre-existent and a possible risk factor for BC. These results indicate that it may be possible to screen for both breast cancer risk and breast cancer activity using a simple blood test.

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Section: Discussionmentioning

confidence: 97%

Plasmalogen Deficiency and Overactive Fatty Acid Elongation Biomarkers in Serum of Breast Cancer Patients Pre- and Post-Surgery—New Insights on Diagnosis, Risk Assessment, and Disease Mechanisms

Tomida

Goodenowe²,

Koyama

et al. 2021

Cancers

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“…It is also not known whether the decrease of PlsEtns in the patients with AD is the cause or the consequence of the disease. It may be both [15], although an earlier suggestion indicated that it may be the cause of the ethology of AD [57]. A few possible mechanisms with regards to the decrease of PlsEtns in AD have been suggested including peroxisome dysfunction, oxidative stress, alterations in membrane lipid rafts and inflammatory responses [2, 3, 42, 58, 59].…”

Section: Association Of Plsetns With Alzheimer’s Disease and Their Pomentioning

confidence: 99%

“…Supplementation with 0.1% PlsEtn for 4 weeks in Zucker diabetic fatty (ZDF) rats and for 9 weeks in healthy Wistar rats reduced the plasma cholesterol and phospholipid concentrations; corresponding with this, an increase in erythrocyte PlsEtn and phosphatidylethanolamine was observed [17]. Oral administration of plasmalogens precursor PPI-1011 (100 mg/kg/day) to C57/6 J mice for 2 weeks restored the reduced levels of PlsEtns in plasma and brain, and this plasmalogen restoration was associated with a stimulated re-myelination of neuronal cells [57].…”

Section: Plasmalogens As a Potential Therapy For Admentioning

confidence: 99%

Plasmalogens and Alzheimer’s disease: a review

2019

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Growing evidence suggests that ethanolamine plasmalogens (PlsEtns), a subtype of phospholipids, have a close association with Alzheimer’s disease (AD). Decreased levels of PlsEtns have been commonly found in AD patients, and were correlated with cognition deficit and severity of disease. Limited studies showed positive therapeutic outcomes with plasmalogens interventions in AD subjects and in rodents. The potential mechanisms underlying the beneficial effects of PlsEtns on AD may be related to the reduction of γ–secretase activity, an enzyme that catalyzes the synthesis of β-amyloid (Aβ), a hallmark of AD. Emerging in vitro evidence also showed that PlsEtns prevented neuronal cell death by enhancing phosphorylation of AKT and ERK signaling through the activation of orphan G-protein coupled receptor (GPCR) proteins. In addition, PlsEtns have been found to suppress the death of primary mouse hippocampal neuronal cells through the inhibition of caspase-9 and caspase-3 cleavages. Further in-depth investigations are required to determine the signature molecular species of PlsEtns associated with AD, hence their potential role as biomarkers. Clinical intervention with plasmalogens is still in its infancy but may have the potential to be explored for a novel therapeutic approach to correct AD pathology and neural function.

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“…Thus, the results obtained by us and other authors show that enrichment of diet with dietary supplements, whose structure contains a simple ether bond and n-3 PUFAs, can compensate for the lack of plasmalogens in the body. Several drugs have been earlier proposed that meet these requirements: These are semisynthetic plasmalogens (Chen & Liu, 2013) or their precur-sors (Wood et al, 2011). However, the multi-stage processes of obtaining and the relatively low yield of final products determine the high costs of such preparations.…”

Section: Discussionmentioning

confidence: 99%

“…One of the ways to improve the quality of life of elderly people can be diet correction by adding biologically active substances that stimulate blood formation and the immune system and regulate lipid metabolism. The n-3 polyunsaturated fatty acids (PUFAs) and alkyl glycerol ethers (AGs) are suggested as very promising in this respect (Wood et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Action of alkyl glycerol ethers and n‐3 polyunsaturated fatty acids diet on hematological parameters of blood and liver plasmalogen level in aged rats

Sultanov

Ermolenko

Poleschuk

et al. 2021

Journal of Food Science

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One of the ways to reduce age‐related changes can be a diet correction by adding biologically active substances. We studied the effect of a diet including alkyl glycerol ethers (AGs) and n‐3 polyunsaturated fatty acid (PUFA) concentrate isolated from the hepatopancreas of Berrytheuthis magister squid on hematological parameters and plasmalogens level in the liver of elderly rats. The senile animals showed decrease in hemoglobin, a three‐fold decrease in leukocytes, a three‐fold increase in platelet count, and a double decrease of blood coagulation time in the peripheral blood. Age‐related changes in rats were characterized by the development of anemia, hypercoagulation, and a decrease in the number of immunocompetent cells. AGs, both separately and in combination with n‐3 PUFAs, induced an increase in the number of red blood cells and hemoglobin, a decrease in the number of platelets, and an immunostimulating activity. Under the action of AGs and n‐3 PUFAs, the concentration of plasmalogens and docosahexaenoic acid in the rat liver increased 2‐ and 1.5 folds, respectively. Practical Application This study showed that the combined use of AGs and n‐3 PUFAs improves the rheological properties of the blood and the state of the immune system during aging. The enrichment of diet with dietary supplements, whose structure contains AGs and n‐3 PUFAs can increase the content of plasmalogens in the body.

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Plasmalogen Deficit: A New and Testable Hypothesis for the Etiology of Alzheimer’s Disease

Cited by 6 publications

References 71 publications

Plasmalogen Deficiency and Overactive Fatty Acid Elongation Biomarkers in Serum of Breast Cancer Patients Pre- and Post-Surgery—New Insights on Diagnosis, Risk Assessment, and Disease Mechanisms

Plasmalogen Deficiency and Overactive Fatty Acid Elongation Biomarkers in Serum of Breast Cancer Patients Pre- and Post-Surgery—New Insights on Diagnosis, Risk Assessment, and Disease Mechanisms

Plasmalogens and Alzheimer’s disease: a review

Action of alkyl glycerol ethers and n‐3 polyunsaturated fatty acids diet on hematological parameters of blood and liver plasmalogen level in aged rats

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