Sphingomyelins and ceramides: possible biomarkers for dementia?

Loft, Laura M I; Moseholm, Kristine F; Pedersen, Karoline K W; Jensen, Majken K.; Koch, Manja; Cronjé, Héléne T.

doi:10.1097/mol.0000000000000804

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…Choline plays a crucial role as a key metabolite necessary to maintain homeostasis between these two lipids 79 . Both LPCs and SMs are choline-containing lipids, although they do not directly share metabolic pathways 80,81 . In this sense, the selective vulnerability of BFCNs in various neurodegenerative diseases might result, in part, from an imbalance between these choline-containing lipids, as choline is used to synthesize both choline-containing lipids and ACh.…”

Section: Discussionmentioning

confidence: 99%

Cortical lipids containing choline mediate cannabinoid-induced cognitive improvement

Moreno-Rodríguez,

Martínez-Gardeazabal,

de Tena

et al. 2024

Preprint

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Recent research connecting choline-containing lipids to basal forebrain cholinergic neurons (BFCN) degeneration in neuropathological states highlights a challenge for balancing lipid integrity with optimal acetylcholine (ACh) levels. Warranting an adequate choline source to maintain ACh levels in this pathway is crucial for preserving memory. The endocannabinoid (eCB) system plays a role in modulating learning and memory processes controlled by cholinergic neurotransmission. Consequently, we propose that activation of this system is neuroprotective against cholinergic degeneration. In the present study, we investigated the neuroprotective effect of a subchronic treatment with the CB1 cannabinoid agonist, WIN55,212-2, using both ex vivo and in vivo 192IgG-Saporin models of specific cholinergic damage. Degeneration of baso-cortical cholinergic pathways induced memory deficits and a downregulation of saturated and mono-unsaturated lysophosphatidylcholines (LPC) cortical levels. WIN55,212-2 not only restored memory deficits but also increased cortical ACh levels and modified cortical choline-containing lipids such as sphingomyelins (SM) and LPCs, which are essential for correct memory functioning, in lesioned animals. Given these results, we propose that WIN55,212-2 generates an alternative choline source through the breakdown of SMs, which is enough to increase cortical ACh levels and LPCs. These findings suggest that modification of choline-containing lipids by the activation of CB1 receptors is a promising therapy for dementia associated with cholinergic dysfunction, such as in Alzheimer's disease (AD).

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Section: Discussionmentioning

confidence: 99%

Cortical lipids containing choline mediate cannabinoid-induced cognitive improvement

Moreno-Rodríguez,

Martínez-Gardeazabal,

de Tena

et al. 2024

Preprint

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“…The balance of sphingomyelins is essential for normal neuronal function and the deficiencies in enzymes of sphingomyelins metabolism can lead to various severe brain disorders. Some researches indicated blood-based sphingomyelins played crucial roles in dementia but the conclusions were inconsistent [ 23 ]. A longitudinal cohort provided evidence for sex-specific associations between sphingomyelins and dementia, which might account for the above inconsistence [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Liquid chromatography-mass spectrometry-based metabolomic profiling reveals sex differences of lipid metabolism among the elderly from Southwest China

Huang

et al. 2023

BMC Geriatr

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Background The sexual dimorphism represents one of the triggers of the metabolic disparities while the identification of sex-specific metabolites in the elderly has not been achieved. Methods A group of aged healthy population from Southwest China were recruited and clinical characteristics were collected. Fasting plasma samples were obtained and untargeted liquid chromatography-mass spectrometry-based metabolomic analyses were performed. Differentially expressed metabolites between males and females were identified from the metabolomic analysis and metabolite sets enrichment analysis was employed. Results Sixteen males and fifteen females were finally enrolled. According to clinical characteristics, no significant differences can be found except for smoking history. There were thirty-six differentially expressed metabolites between different sexes, most of which were lipids and lipid-like molecules. Twenty-three metabolites of males were increased while thirteen were decreased compared with females. The top four classes of metabolites were fatty acids and conjugates (30.6%), glycerophosphocholines (22.2%), sphingomyelins (11.1%), and flavonoids (8.3%). Fatty acids and conjugates, glycerophosphocholines, and sphingomyelins were significantly enriched in metabolite sets enrichment analysis. Conclusions Significant lipid metabolic differences were found between males and females among the elderly. Fatty acids and conjugates, glycerophosphocholines, and sphingomyelins may partly account for sex differences and can be potential treatment targets for sex-specific diseases.

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“…In addition, SM/ceramide has been related to AD cognitive decline [ 10 ]. However, the utility of ceramides as biomarkers for dementias requires further investigation [ 28 ]. LPE was described as a biomarker for progression to AD [ 9 ], although our results suggest that it could be a potential biomarker for preclinical stages.…”

Section: Discussionmentioning

confidence: 99%

Plasma Lipidomics Approach in Early and Specific Alzheimer’s Disease Diagnosis

Peña-Bautista

Álvarez-Sánchez

Roca

et al. 2022

JCM

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Background: The brain is rich in lipid content, so a physiopathological pathway in Alzheimer’s disease (AD) could be related to lipid metabolism impairment. The study of lipid profiles in plasma samples could help in the identification of early AD changes and new potential biomarkers. Methods: An untargeted lipidomic analysis was carried out in plasma samples from preclinical AD (n = 11), mild cognitive impairment-AD (MCI-AD) (n = 31), and healthy (n = 20) participants. Variables were identified by means of two complementary methods, and lipid families’ profiles were studied. Then, a targeted analysis was carried out for some identified lipids. Results: Statistically significant differences were obtained for the diglycerol (DG), lysophosphatidylethanolamine (LPE), lysophosphatidylcholine (LPC), monoglyceride (MG), and sphingomyelin (SM) families as well as for monounsaturated (MUFAs) lipids, among the participant groups. In addition, statistically significant differences in the levels of lipid families (ceramides (Cer), LPE, LPC, MG, and SM) were observed between the preclinical AD and healthy groups, while statistically significant differences in the levels of DG, MG, and PE were observed between the MCI-AD and healthy groups. In addition, 18:1 LPE showed statistically significant differences in the targeted analysis between early AD (preclinical and MCI) and healthy participants. Conclusion: The different plasma lipid profiles could be useful in the early and minimally invasive detection of AD. Among the lipid families, relevant results were obtained from DGs, LPEs, LPCs, MGs, and SMs. Specifically, MGs could be potentially useful in AD detection; while LPEs, LPCs, and SM seem to be more related to the preclinical stage, while DGs are more related to the MCI stage. Specifically, 18:1 LPE showed a potential utility as an AD biomarker.

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Sphingomyelins and ceramides: possible biomarkers for dementia?

Cited by 7 publications

References 29 publications

Cortical lipids containing choline mediate cannabinoid-induced cognitive improvement

Cortical lipids containing choline mediate cannabinoid-induced cognitive improvement

Liquid chromatography-mass spectrometry-based metabolomic profiling reveals sex differences of lipid metabolism among the elderly from Southwest China

Plasma Lipidomics Approach in Early and Specific Alzheimer’s Disease Diagnosis

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