Plasma metabolomics in early Alzheimer's disease patients diagnosed with amyloid biomarker

Peña-Bautista, Carmen; Roca, Marta; Hervás, David; Cuevas, Ana; López‐Cuevas, Rogelio; Vento, Máximo; Baquero, Miguel; García‐Blanco, Ana; Cháfer-Pericás, Consuelo

doi:10.1016/j.jprot.2019.04.008

Cited by 51 publications

(40 citation statements)

References 59 publications

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“…In one such study, the authors utilized untargeted metabolomics of cerebrospinal fluid (CSF) from control subjects or subjects with stable mild cognitive impairment (MCI), MCI that progressed into AD, or AD and identified 17 biomarkers capable of predicting the development of AD with an accuracy of 98.7% [145]. This and other metabolomics studies [146][147][148][149][150] of AD patient samples not only provide great potential for developing methods for early diagnosis in AD, but also provide a potential mechanism to validate AD-like COs and other ND organoid models to ensure that they recapitulate the phenotypes seen in humans.…”

Section: Metabolomicsmentioning

confidence: 99%

Modeling neurodegenerative diseases with cerebral organoids and other three-dimensional culture systems: focus on Alzheimer’s disease

Venkataraman

Fair

McElroy

et al. 2020

Stem Cell Rev and Rep

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Section: Metabolomicsmentioning

confidence: 99%

Modeling neurodegenerative diseases with cerebral organoids and other three-dimensional culture systems: focus on Alzheimer’s disease

Venkataraman

Fair

McElroy

et al. 2020

Stem Cell Rev and Rep

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“…Both procedures are invasive, and the findings are usually conclusive only several years after the establishment of dementia [ 67 , 68 ]. Due to these findings, the search for AD biomarkers initially has been concentrated mainly in the CSF and brain tissues [ 64 ].…”

Section: Metabolites In Specific Neurological Diseasesmentioning

confidence: 99%

“…A comparison between 29 patients diagnosed with MCI who subsequently developed AD (MCI-AD) and 29 healthy individuals indicated that lysophosphatidylethanolamine, named LysoPE (20:0/0:0)/LysoPE (0:0/20:0), choline, and soraphen A, might be potential early AD biomarkers in plasma; all were increased in the MCI-AD group [ 68 ]. Although soraphen A is a myxobacteria product, and its interaction with AD should be better studied, it is currently known that it is related to increased short-chain fatty acids (FA) and choline levels due to its capacity to inhibit acetyl-CoA carboxylase and avoid FA elongation [ 68 ]. Moreover, the data specified choline as the best bet for a promising biomarker in early AD diagnosis; it was the only confirmed metabolite based on its pure standard.…”

Section: Metabolites In Specific Neurological Diseasesmentioning

confidence: 99%

“…Moreover, the data specified choline as the best bet for a promising biomarker in early AD diagnosis; it was the only confirmed metabolite based on its pure standard. Choline plays an essential role in neurotransmitter pathways as the acetylcholine precursor, as well as in some lipids that are related to brain function, such as phosphatidylcholine [ 68 ].…”

Section: Metabolites In Specific Neurological Diseasesmentioning

confidence: 99%

“…In addition, it is also possible to observe the involvement of harmful oxidative processes, with the potential to affect membranes, as has already been proposed for Lysophosphatidic acid C18: 2 in patients with AD [ 71 ]. Furthermore, carnitine and the related metabolite acetylcarnitine, an intermediary of fatty acid oxidation, were found in studies on AD, ALS, MS, and stroke and related to impairment mitochondrial and energy metabolisms and fatty acids transport during the catabolism of lipids [ 9 , 68 , 83 , 109 ]. Because of the acetyl group, the acetylcarnitine can cross the blood–brain barrier more easily and is the preferred form in the central nervous system [ 9 ].…”

Section: Metabolites In Specific Neurological Diseasesmentioning

confidence: 99%

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Circulating Metabolites as Potential Biomarkers for Neurological Disorders—Metabolites in Neurological Disorders

et al. 2020

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There are, still, limitations to predicting the occurrence and prognosis of neurological disorders. Biomarkers are molecules that can change in different conditions, a feature that makes them potential tools to improve the diagnosis of disease, establish a prognosis, and monitor treatments. Metabolites can be used as biomarkers, and are small molecules derived from the metabolic process found in different biological media, such as tissue samples, cells, or biofluids. They can be identified using various strategies, targeted or untargeted experiments, and by different techniques, such as high-performance liquid chromatography, mass spectrometry, or nuclear magnetic resonance. In this review, we aim to discuss the current knowledge about metabolites as biomarkers for neurological disorders. We will present recent developments that show the need and the feasibility of identifying such biomarkers in different neurological disorders, as well as discuss relevant research findings in the field of metabolomics that are helping to unravel the mechanisms underlying neurological disorders. Although several relevant results have been reported in metabolomic studies in patients with neurological diseases, there is still a long way to go for the clinical use of metabolites as potential biomarkers in these disorders, and more research in the field is needed.

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High‐resolution metabolomic profiling of Alzheimer’s disease in plasma

Niedzwiecki

Walker

Howell

et al. 2019

Ann Clin Transl Neurol

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BackgroundAlzheimer’s disease (AD) is a complex neurological disorder with contributions from genetic and environmental factors. High‐resolution metabolomics (HRM) has the potential to identify novel endogenous and environmental factors involved in AD. Previous metabolomics studies have identified circulating metabolites linked to AD, but lack of replication and inconsistent diagnostic algorithms have hindered the generalizability of these findings. Here we applied HRM to identify plasma metabolic and environmental factors associated with AD in two study samples, with cerebrospinal fluid (CSF) biomarkers of AD incorporated to achieve high diagnostic accuracy.MethodsLiquid chromatography‐mass spectrometry (LC–MS)‐based HRM was used to identify plasma and CSF metabolites associated with AD diagnosis and CSF AD biomarkers in two studies of prevalent AD (Study 1: 43 AD cases, 45 mild cognitive impairment [MCI] cases, 41 controls; Study 2: 50 AD cases, 18 controls). AD‐associated metabolites were identified using a metabolome‐wide association study (MWAS) framework.ResultsAn MWAS meta‐analysis identified three non‐medication AD‐associated metabolites in plasma, including elevated levels of glutamine and an unknown halogenated compound and lower levels of piperine, a dietary alkaloid. The non‐medication metabolites were correlated with CSF AD biomarkers, and glutamine and the unknown halogenated compound were also detected in CSF. Furthermore, in Study 1, the unknown compound and piperine were altered in MCI patients in the same direction as AD dementia.ConclusionsIn plasma, AD was reproducibly associated with elevated levels of glutamine and a halogen‐containing compound and reduced levels of piperine. These findings provide further evidence that exposures and behavior may modify AD risks.

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Plasma metabolomics in early Alzheimer's disease patients diagnosed with amyloid biomarker

Cited by 51 publications

References 59 publications

Modeling neurodegenerative diseases with cerebral organoids and other three-dimensional culture systems: focus on Alzheimer’s disease

Modeling neurodegenerative diseases with cerebral organoids and other three-dimensional culture systems: focus on Alzheimer’s disease

Circulating Metabolites as Potential Biomarkers for Neurological Disorders—Metabolites in Neurological Disorders

High‐resolution metabolomic profiling of Alzheimer’s disease in plasma

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