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Metabolites
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Lipid Biomarkers in Alzheimer's Disease
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Lipid Biomarkers in Alzheimer's Disease

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (15 April 2022) | Viewed by 13997

Special Issue Editor

Prof. Dr. Yoshiya Oda

E-Mail Website
Guest Editor
Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
Interests: clinical biomarkers; proteomics; metabolomics; lipidomics; diagnosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The number of patients with dementia is increasing as the population ages in many countries. Dementia can be subdivided into several categories and Alzheimer's disease (AD) accounts for about 70% of dementia patients. Although AD research is being conducted vigorously all over the world, the pathogenesis of AD is still largely unknown and the lack of a fundamental cure or appropriate early diagnosis places AD among the diseases with the highest unmet needs. Apolipoprotein E4 (APOE4) is known to be a strong risk factor for the development of AD. APOE is a member of the family of lipid-binding proteins, which are involved in lipid metabolism and a major transporter of cholesterol in the brain. Several studies have also shown that polyunsaturated fatty acid (PUFA) intake reduces the risk of Alzheimer's disease. Aspirin, which inhibits cyclooxygenase, an enzyme involved in the metabolism of arachidonic acid has long been claimed to be effective in preventing AD. It is also said that the effect of aspirin on AD is mediated by proliferator-activated receptor alpha (PPAR alpha), a receptor activated by free fatty acids. Furthermore, amyloid protein has been the main focus of AD research, and its precursor, amyloid precursor protein (APP), is a membrane protein. Lipids are the major components of membranes. Thus, there is a high possibility that lipids are related to AD. Therefore, we have planned a Special Issue on Lipid Biomarkers in Alzheimer's disease.

Prof. Dr. Yoshiya Oda
Guest Editor

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Keywords

  • Lipid biomarkers for Alzheimer’s disease
  • Lipid metabolism in Alzheimer’s disease
  • Lipidomics for Alzheimer’s disease
  • Biomarker technology platforms
  • Dietary lipids and Alzheimer’s disease prevention

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Published Papers (4 papers)

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Research

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18 pages, 3031 KiB  
Article
Liver and White/Brown Fat Dystrophy Associates with Gut Microbiota and Metabolomic Alterations in 3xTg Alzheimer’s Disease Mouse Model
by Maria Angela Guzzardi, Federica La Rosa, Daniela Campani, Maria Carmen Collado, Daniel Monleon, Andrea Cacciato Insilla, Maria Tripodi, Alessandro Zega, Alessia Dattilo, Maurizia Rossana Brunetto, Margherita Maffei, Ferruccio Bonino and Patricia Iozzo
Metabolites 2022, 12(4), 278; https://doi.org/10.3390/metabo12040278 - 22 Mar 2022
Viewed by 4166
Abstract
Metabolic impairments and liver and adipose depots alterations were reported in subjects with Alzheimer’s disease (AD), highlighting the role of the liver–adipose–tissue–brain axis in AD pathophysiology. The gut microbiota might play a modulating role. We investigated the alterations to the liver and white/brown [...] Read more.
Metabolic impairments and liver and adipose depots alterations were reported in subjects with Alzheimer’s disease (AD), highlighting the role of the liver–adipose–tissue–brain axis in AD pathophysiology. The gut microbiota might play a modulating role. We investigated the alterations to the liver and white/brown adipose tissues (W/BAT) and their relationships with serum and gut metabolites and gut bacteria in a 3xTg mouse model during AD onset (adulthood) and progression (aging) and the impact of high-fat diet (HFD) and intranasal insulin (INI). Glucose metabolism (18FDG-PET), tissue radiodensity (CT), liver and W/BAT histology, BAT-thermogenic markers were analyzed. 16S-RNA sequencing and mass-spectrometry were performed in adult (8 months) and aged (14 months) 3xTg-AD mice with a high-fat or control diet. Generalized and HFD resistant deficiency of lipid accumulation in both liver and W/BAT, hypermetabolism in WAT (adulthood) and BAT (aging), abnormal cytokine–hormone profiles, and liver inflammation were observed in 3xTg mice; INI could antagonize all these alterations. Specific gut microbiota–metabolome profiles correlated with a significant disruption of the gut–microbiota–liver–adipose axis in AD mice. In conclusion, fat dystrophy in liver and adipose depots contributes to AD progression, and associates with altered profiles of the gut microbiota, which candidates as an appealing early target for preventive intervention. Full article
(This article belongs to the Special Issue Lipid Biomarkers in Alzheimer's Disease)
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13 pages, 2114 KiB  
Article
Association between Visceral Adipose Tissue Metabolism and Alzheimer’s Disease Pathology
by Shin Kim, Hyon-Ah Yi, Kyoung Sook Won, Ji Soo Lee and Hae Won Kim
Metabolites 2022, 12(3), 258; https://doi.org/10.3390/metabo12030258 - 17 Mar 2022
Cited by 16 | Viewed by 2682
Abstract
The visceral adipose tissue (VAT) has been recognized as an endocrine organ, and VAT dysfunction could be a risk factor for Alzheimer’s disease (AD). We aimed to evaluate the association of VAT metabolism with AD pathology. This cross-sectional study included 54 older subjects [...] Read more.
The visceral adipose tissue (VAT) has been recognized as an endocrine organ, and VAT dysfunction could be a risk factor for Alzheimer’s disease (AD). We aimed to evaluate the association of VAT metabolism with AD pathology. This cross-sectional study included 54 older subjects with cognitive impairment who underwent 2-deoxy-2-[fluorine-18]-fluoro-D-glucose (18F-FDG) torso positron emission tomography (PET) and 18F-florbetaben brain PET. 18F-FDG uptake in VAT on 18F-FDG PET images was used as a marker of VAT metabolism, and subjects were classified into high and low VAT metabolism groups. A voxel-based analysis revealed that the high VAT metabolism group exhibited a significantly higher cerebral amyloid-β (Aβ) burden than the low VAT metabolism group. In the volume-of-interest analysis, multiple linear regression analyses with adjustment for age, sex, and white matter hyperintensity volume revealed that 18F-FDG uptake in VAT was significantly associated with the cerebral Aβ burden (β = 0.359, p = 0.007). In conclusion, VAT metabolism was associated with AD pathology in older subjects. Our findings suggest that VAT dysfunction could contribute to AD development. Full article
(This article belongs to the Special Issue Lipid Biomarkers in Alzheimer's Disease)
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Review

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25 pages, 1866 KiB  
Review
A Review of Oxylipins in Alzheimer’s Disease and Related Dementias (ADRD): Potential Therapeutic Targets for the Modulation of Vascular Tone and Inflammation
by Lynne H. Shinto, Jacob Raber, Anusha Mishra, Natalie Roese and Lisa C. Silbert
Metabolites 2022, 12(9), 826; https://doi.org/10.3390/metabo12090826 - 1 Sep 2022
Cited by 11 | Viewed by 3290
Abstract
There is now a convincing body of evidence from observational studies that the majority of modifiable Alzheimer’s disease and related dementia (ADRD) risk factors are vascular in nature. In addition, the co-existence of cerebrovascular disease with AD is more common than AD alone, [...] Read more.
There is now a convincing body of evidence from observational studies that the majority of modifiable Alzheimer’s disease and related dementia (ADRD) risk factors are vascular in nature. In addition, the co-existence of cerebrovascular disease with AD is more common than AD alone, and conditions resulting in brain ischemia likely promote detrimental effects of AD pathology. Oxylipins are a class of bioactive lipid mediators derived from the oxidation of long-chain polyunsaturated fatty acids (PUFAs) which act as modulators of both vascular tone and inflammation. In vascular cognitive impairment (VCI), there is emerging evidence that oxylipins may have both protective and detrimental effects on brain structure, cognitive performance, and disease progression. In this review, we focus on oxylipin relationships with vascular and inflammatory risk factors in human studies and animal models pertinent to ADRD. In addition, we discuss future research directions with the potential to impact the trajectory of ADRD risk and disease progression. Full article
(This article belongs to the Special Issue Lipid Biomarkers in Alzheimer's Disease)
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14 pages, 317 KiB  
Review
Mass Spectrometry-Based Analysis of Lipid Involvement in Alzheimer’s Disease Pathology—A Review
by Andrea R. Kelley
Metabolites 2022, 12(6), 510; https://doi.org/10.3390/metabo12060510 - 2 Jun 2022
Cited by 1 | Viewed by 2666
Abstract
Irregularities in lipid metabolism have been linked to numerous neurodegenerative diseases. The roles of abnormal brain, plasma, and cerebrospinal fluid (CSF) lipid levels in Alzheimer’s disease (AD) onset and progression specifically have been described to a great extent in the literature. Apparent hallmarks [...] Read more.
Irregularities in lipid metabolism have been linked to numerous neurodegenerative diseases. The roles of abnormal brain, plasma, and cerebrospinal fluid (CSF) lipid levels in Alzheimer’s disease (AD) onset and progression specifically have been described to a great extent in the literature. Apparent hallmarks of AD include, but are not limited to, genetic predisposition involving the APOE Ɛ4 allele, oxidative stress, and inflammation. A common culprit tied to many of these hallmarks is disruption in brain lipid homeostasis. Therefore, it is important to understand the roles of lipids, under normal and abnormal conditions, in each process. Lipid influences in processes such as inflammation and blood–brain barrier (BBB) disturbance have been primarily studied via biochemical-based methods. There is a need, however, for studies focused on uncovering the relationship between lipid irregularities and AD by molecular-based quantitative analysis in transgenic animal models and human samples alike. In this review, mass spectrometry as it has been used as an analytical tool to address the convoluted relationships mentioned above is discussed. Additionally, molecular-based mass spectrometry strategies that should be used going forward to further relate structure and function relationships of lipid irregularities and hallmark AD pathology are outlined. Full article
(This article belongs to the Special Issue Lipid Biomarkers in Alzheimer's Disease)
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