Plasma Lipids as Biomarkers for Alzheimer's Disease: A Systematic Review

Agarwal, Mehak; Khan, Safeera

doi:10.7759/cureus.12008

Cited by 51 publications

(53 citation statements)

References 49 publications

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“…However, the variation tendency of these metabolites in the CNS appears to be different from our previous observation in the periphery. These conflicting findings may be caused by the BBB, which maintains CNS homeostasis by regulating the transport of solutes between blood and brain (41). The lipids in the brain and periphery are two units that are separated by the BBB.…”

Section: Discussionmentioning

confidence: 99%

Lipid Metabolism in the Development and Progression of Vascular Cognitive Impairment: A Systematic Review

et al. 2021

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Background: Vascular cognitive impairment (VCI) is a major public health problem. The current diagnosis of VCI is made based on the assessment of clinical symptoms and neuropsychological measurements, and is supported by neuroimaging. These methods are both time-consuming and expensive, which leads to needs for alternative biomarkers for VCI. Metabolomics is an emerging and powerful tool to discover of new biomarkers of disease, which can investigate variations in different metabolic processes such as lipid, since the brain is highly enriched in lipids and that lipid changes may lead to pathology in the brain. Vascular cognitive impairment is vulnerable to the disturbance of lipid metabolism. Furthermore, blood samples, which could be identified as reliable clinical biomarkers are relatively convenient to obtain and provide a non-invasive assessment. Therefore, our study aims to understand whether peripheral lipid biomarkers can be used as diagnostic biomarkers and monitor the progression of VCI.Methods: We systematically searched the PubMed, Embase, CNKI, and VIP databases to find VCI and lipid metabolism in reports from inception through February 2021. Studies meeting the following criteria were eligible: (1) original studies in humans; (2) lipid metabolites in blood; (3) reports of VCI.Results: Through our review, nine original articles were eligible. Blood-based metabolites that might be potential biomarkers were identified. Most of them including PC, PE, Cers, and ChEs were significantly lower, while elevation of FAs and DGs were associated with VCI. Most importantly, these blood-based metabolites might be proposed as potential biomarkers for VCI, which provides direction for further validation.Discussion and Conclusion: To the best of our knowledge, this is the first systemic review concerning the relationship of lipid metabolism and VCI. It identifies potential biomarkers and provides insights into the disease pathobiology. However, more advanced studies and researches on a lipidomic platform must be done to understand the exact pathology behind and identify potential lipid biomarkers, which might help achieve the goal of discovering novel therapeutics.

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Section: Discussionmentioning

confidence: 99%

Lipid Metabolism in the Development and Progression of Vascular Cognitive Impairment: A Systematic Review

et al. 2021

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“…The useful adoption of 24OHC and 27OHC measurements in CSF was further confirmed as an additional reliable biomarker of AD [ 48 ], and their quantification also in blood serum/plasma suggested [ 42 , 49 , 50 ].…”

Section: Medical Laboratory Industry: Oxysterols As Possible Diagnostic Markersmentioning

confidence: 99%

Oxysterols: From redox bench to industry

et al. 2022

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More and more attention is nowadays given to the possible translational application of a great number of biochemical and biological findings with the involved molecules. This is also the case of cholesterol oxidation products, redox molecules over the last years deeply investigated for their implication in human pathophysiology. Oxysterols of non-enzymatic origin, the excessive increase of which in biological fluids and tissues is of toxicological relevance for their marked pro-oxidant and pro-inflammatory properties, are increasingly applied in clinical biochemistry as molecular markers in the diagnosis and monitoring of several human and veterinary diseases. Conversely, oxysterols of enzymatic origin, the production of which is commonly under physiological regulation, could be considered and tested as promising pharmaceutical agents because of their antiviral, pro-osteogenic and antiadipogenic properties of some of them. Very recently, the quantification of oxysterols of non-enzymatic origin has been adopted in a systematic way to evaluate, monitor and improve the quality of cholesterol-based food ingredients, that are prone to auto-oxidation, as well as their industrial processing and the packaging and the shelf life of the finished food products. The growing translational value of oxysterols is here reviewed in its present and upcoming applications in various industrial fields.

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“…A relationship between AD progression and 24-OHC, as well as other plasma lipids (HDL, LDL, total serum cholesterol, 27-OHC, triglycerides, lipoprotein A, phospholipids, and sphingolipids), has been observed [ 71 ]. This evidence supports the association between hypercholesterolemia/dyslipidemia and increased plasma levels of 24-OHC.…”

Section: 24-ohc Levels In Alzheimer’s Disease Biological Samplesmentioning

confidence: 99%

The Controversial Role of 24-S-Hydroxycholesterol in Alzheimer’s Disease

et al. 2021

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The development of Alzheimer’s disease (AD) is influenced by several events, among which the dysregulation of cholesterol metabolism in the brain plays a major role. Maintenance of brain cholesterol homeostasis is essential for neuronal functioning and brain development. To maintain the steady-state level, excess brain cholesterol is converted into the more hydrophilic metabolite 24-S-hydroxycholesterol (24-OHC), also called cerebrosterol, by the neuron-specific enzyme CYP46A1. A growing bulk of evidence suggests that cholesterol oxidation products, named oxysterols, are the link connecting altered cholesterol metabolism to AD. It has been shown that the levels of some oxysterols, including 27-hydroxycholesterol, 7β-hydroxycholesterol and 7-ketocholesterol, significantly increase in AD brains contributing to disease progression. In contrast, 24-OHC levels decrease, likely due to neuronal loss. Among the different brain oxysterols, 24-OHC is certainly the one whose role is most controversial. It is the dominant oxysterol in the brain and evidence shows that it represents a signaling molecule of great importance for brain function. However, numerous studies highlighted the potential role of 24-OHC in favoring AD development, since it promotes neuroinflammation, amyloid β (Aβ) peptide production, oxidative stress and cell death. In parallel, 24-OHC has been shown to exert several beneficial effects against AD progression, such as preventing tau hyperphosphorylation and Aβ production. In this review we focus on the current knowledge of the controversial role of 24-OHC in AD pathogenesis, reporting a detailed overview of the findings about its levels in different AD biological samples and its noxious or neuroprotective effects in the brain. Given the relevant role of 24-OHC in AD pathophysiology, its targeting could be useful for disease prevention or slowing down its progression.

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Plasma Lipids as Biomarkers for Alzheimer's Disease: A Systematic Review

Cited by 51 publications

References 49 publications

Lipid Metabolism in the Development and Progression of Vascular Cognitive Impairment: A Systematic Review

Lipid Metabolism in the Development and Progression of Vascular Cognitive Impairment: A Systematic Review

Oxysterols: From redox bench to industry

The Controversial Role of 24-S-Hydroxycholesterol in Alzheimer’s Disease

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