Lipid metabolism in Alzheimer’s disease

Zhu, Tian-Bi; Zhao, Zi‐Gang; Luo, Piao; Wang, Shasha; Peng, Ye; Chu, Shifeng; Chen, Nai‐Hong

doi:10.1016/j.brainresbull.2018.11.012

Cited by 44 publications

(27 citation statements)

References 111 publications

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“…In addition, ZBTB20 is another upstream regulator that plays an essential role in glucose homeostasis 49 . Thus our results give several indications of a dysfunctional energy metabolism in AD 11,26,33,37,50,51 …”

Section: Discussionsupporting

confidence: 58%

“…49 Thus our results give several indications of a dysfunctional energy metabolism in AD. 11,26,33,37,50,51 In the context of inflammation, astrocytes and microglia are the principal players in AD 26,52 and their activation is characteristic of the preclinical phase. 53 Ab activates microglia (Brain resident macrophages 54 which trigger a proinflammatory cascade, likely IL-12, and IL-23.…”

Section: Discussionmentioning

confidence: 99%

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Plasma metabolomics of presymptomatic PSEN1‐H163Y mutation carriers: a pilot study

Natarajan

Ullgren

Khoshnood

et al. 2021

Ann Clin Transl Neurol

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Background and Objective PSEN1‐H163Y carriers, at the presymptomatic stage, have reduced 18FDG‐PET binding in the cerebrum of the brain (Scholl et al., Neurobiol Aging 32:1388–1399, 2011). This could imply dysfunctional energy metabolism in the brain. In this study, plasma of presymptomatic PSEN1 mutation carriers was analyzed to understand associated metabolic changes. Methods We analyzed plasma from noncarriers (NC, n = 8) and presymptomatic PSEN1‐H163Y mutation carriers (MC, n = 6) via untargeted metabolomics using gas and liquid chromatography coupled with mass spectrometry, which identified 1199 metabolites. All the metabolites were compared between MC and NC using univariate analysis, as well as correlated with the ratio of Aβ1–42/Aβ1–40, using Spearman’s correlation. Altered metabolites were subjected to Ingenuity Pathway Analysis (IPA). Results Based on principal component analysis the plasma metabolite profiles were divided into dataset A and dataset B. In dataset A, when comparing between presymptomatic MC and NC, the levels of 79 different metabolites were altered. Out of 79, only 14 were annotated metabolites. In dataset B, 37 metabolites were significantly altered between presymptomatic MC and NC and nine metabolites were annotated. In both datasets, annotated metabolites represent amino acids, fatty acyls, bile acids, hexoses, purine nucleosides, carboxylic acids, and glycerophosphatidylcholine species. 1‐docosapentaenoyl‐GPC was positively correlated, uric acid and glucose were negatively correlated with the ratio of plasma Aβ1–42/Aβ1–40 (P < 0.05). Interpretation This study finds dysregulated metabolite classes, which are changed before the disease symptom onset. Also, it provides an opportunity to compare with sporadic Alzheimer’s Disease. Observed findings in this study need to be validated in a larger and independent Familial Alzheimer’s Disease (FAD) cohort.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Plasma metabolomics of presymptomatic PSEN1‐H163Y mutation carriers: a pilot study

Natarajan

Ullgren

Khoshnood

et al. 2021

Ann Clin Transl Neurol

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“…Congruently, high-fat diet causes a significant elevation of LPA in mouse cortex after eight weeks of high-fat diet [280]. Importantly, over-nutritious food has detrimental effects on brain plasticity because brain diseases could be linked to dysregulated lipid metabolism [281,282,283,284,285,286]. The effects of palmitoleic acid and lysophosphatidic acid on brain health warrant further investigation.…”

Section: Novel Adipocyte-derived Messengers On Brain Healthmentioning

confidence: 99%

The Novel Perspectives of Adipokines on Brain Health

Lee

Cheng

Hoo

et al. 2019

IJMS

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First seen as a fat-storage tissue, the adipose tissue is considered as a critical player in the endocrine system. Precisely, adipose tissue can produce an array of bioactive factors, including cytokines, lipids, and extracellular vesicles, which target various systemic organ systems to regulate metabolism, homeostasis, and immune response. The global effects of adipokines on metabolic events are well defined, but their impacts on brain function and pathology remain poorly defined. Receptors of adipokines are widely expressed in the brain. Mounting evidence has shown that leptin and adiponectin can cross the blood–brain barrier, while evidence for newly identified adipokines is limited. Significantly, adipocyte secretion is liable to nutritional and metabolic states, where defective circuitry, impaired neuroplasticity, and elevated neuroinflammation are symptomatic. Essentially, neurotrophic and anti-inflammatory properties of adipokines underlie their neuroprotective roles in neurodegenerative diseases. Besides, adipocyte-secreted lipids in the bloodstream can act endocrine on the distant organs. In this article, we have reviewed five adipokines (leptin, adiponectin, chemerin, apelin, visfatin) and two lipokines (palmitoleic acid and lysophosphatidic acid) on their roles involving in eating behavior, neurotrophic and neuroprotective factors in the brain. Understanding and regulating these adipokines can lead to novel therapeutic strategies to counteract metabolic associated eating disorders and neurodegenerative diseases, thus promote brain health.

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“…The genetic linkage and association studies have identi ed some AD susceptibility genes, a number of which are related to cholesterol metabolism or transport [3,17,32]. Lipid metabolism play an important pathway involved in the development of AD [32,33]. However, contradictory evidence comes from epidemiological studies showing no or controversial association between dyslipidemia and AD risk [34][35][36].…”

Section: Discussionmentioning

confidence: 99%

Leveraging DNA methylation quantitative-trait loci to characterize the relationship between metabolic traits and Alzheimer’s disease

Liu¹,

Yu²,

Cao³

et al. 2020

Preprint

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Abstract Background: The relationship between DNA methylation, common metabolic risk and Alzheimer’s disease (AD) is not well understood.Methods: Summary statistics integrating DNA methylation quantitative trait loci (mQTLs) and several genome-wide association study data were used. Network with bidirectional mendelian randomization (MR) analysis was performed to examine the causal association among metabolic traits, DNA methylation and AD.Results: Our study showed that cis-mQTLs determined DNA methylation to higher total cholesterol (TC) was associated with higher AD risk (β [95% CI] =0.007 [0.002-0.013], P=0.005). The findings were robust in sensitivity analyses with different instrumental variables. We found no evidence to support causal associations of cis-mQTLs determined obesity and T2D with AD, and vice versa.Conclusion: Overall, our study showed that the cis-mQTLs determined DNA methylation to higher TC was associated with higher AD risk, whereas the relation of cis-mQTLs determined AD and metabolic dysregulation was unlikely to be causal.

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Lipid metabolism in Alzheimer’s disease

Cited by 44 publications

References 111 publications

Plasma metabolomics of presymptomatic PSEN1‐H163Y mutation carriers: a pilot study

Plasma metabolomics of presymptomatic PSEN1‐H163Y mutation carriers: a pilot study

The Novel Perspectives of Adipokines on Brain Health

Leveraging DNA methylation quantitative-trait loci to characterize the relationship between metabolic traits and Alzheimer’s disease

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