Lipidomics of Human Brain Aging and Alzheimer's Disease Pathology

Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victòria; Gonzalo, Hugo; Portero‐Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

doi:10.1016/bs.irn.2015.05.008

Cited by 150 publications

(179 citation statements)

References 193 publications

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“…In addition to evolutionary considerations, brain neurons offer a diverse response to stresses during the physiological aging process or as a result of both NDD and NPD (Mattson and Magnus, 2006; Jové et al, 2014; Naudí et al, 2015). The morphological and functional diversity among neuronal cells, the temporal trajectory of functional losses during the aging process, and the temporal pattern and specificity in the appearance and development of each NDD and NPD, as well as the heterogeneity in neuronal responses to detrimental processes associated with each of the pathologies, all confirm the existence of a cross-regional SNV (Mattson and Magnus, 2006; Jové et al, 2014; Naudí et al, 2015). This SNV could be expressed through a neuron(region)-specific metabolomic profile.…”

Section: Discussionmentioning

confidence: 99%

Specific Metabolomics Adaptations Define a Differential Regional Vulnerability in the Adult Human Cerebral Cortex

Cabré

Jové

Naudí

et al. 2016

Front. Mol. Neurosci.

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Brain neurons offer diverse responses to stresses and detrimental factors during development and aging, and as a result of both neurodegenerative and neuropsychiatric disorders. This multiplicity of responses can be ascribed to the great diversity among neuronal populations. Here we have determined the metabolomic profile of three healthy adult human brain regions—entorhinal cortex, hippocampus, and frontal cortex—using mass spectrometry-based technologies. Our results show the existence of a lessened energy demand, mitochondrial stress, and lower one-carbon metabolism (particularly restricted to the methionine cycle) specifically in frontal cortex. These findings, along with the better antioxidant capacity and lower mTOR signaling also seen in frontal cortex, suggest that this brain region is especially resistant to stress compared to the entorhinal cortex and hippocampus, which are more vulnerable regions. Globally, our results show the presence of specific metabolomics adaptations in three mature, healthy human brain regions, confirming the existence of cross-regional differences in cell vulnerability in the human cerebral cortex.

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Section: Discussionmentioning

confidence: 99%

Specific Metabolomics Adaptations Define a Differential Regional Vulnerability in the Adult Human Cerebral Cortex

Cabré

Jové

Naudí

et al. 2016

Front. Mol. Neurosci.

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“…To this diversity in spatial distribution must be added the temporal factor. Thus, the lipid profile varies in time according with a circadian rhythmicity (Aviram et al, 2016), as well as during the life cycle of an organism (Naudí et al, 2015; Jové et al, 2017). …”

Section: Introductionmentioning

confidence: 99%

“…Thus, a large number of human pathologies are linked to alterations of lipid homeostasis including in addition to a number of genetic disorders (Hobbs et al, 1992), common diseases such as obesity and diabetes (Huynh et al, 2017), cardiovascular disease (Kolovou et al, 2015), cancer (Yang and Han, 2016), and neurodegenerative disease (Naudí et al, 2015; Huynh et al, 2017), among others.…”

Section: Introductionmentioning

confidence: 99%

Lipidomics Reveals a Tissue-Specific Fingerprint

et al. 2018

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In biological systems lipids generate membranes and have a key role in cell signaling and energy storage. Therefore, there is a wide diversity of molecular lipid expressed at the compositional level in cell membranes and organelles, as well as in tissues, whose lipid distribution remains unclear. Here, we report a mass spectrometry study of lipid abundance across 7 rat tissues, detecting and quantifying 652 lipid molecular species from the glycerolipid, glycerophospholipid, fatty acyl, sphingolipid, sterol lipid and prenol lipid categories. Our results demonstrate that every tissue analyzed presents a specific lipid distribution and concentration. Thus, glycerophospholipids are the most abundant tissue lipid, they share a similar tissue distribution but differ in particular lipid species between tissues. Sphingolipids are more concentrated in the renal cortex and sterol lipids can be found mainly in both liver and kidney. Both types of white adipose tissue, visceral and subcutaneous, are rich in glycerolipids but differing the amount. Acylcarnitines are mainly in the skeletal muscle, gluteus and soleus, while heart presents higher levels of ubiquinone than other tissues. The present study demonstrates the existence of a rat tissue-specific fingerprint.

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“…HFD also profoundly affects lipid metabolism and lipid composition in the brain 13, 14 . Thus, it has been suggested that altered lipid metabolism is closely connected to the development and progression of Alzheimer’s disease pathology 15, 16 . Recent studies examining the effect of HFD on phenotype, have demonstrated significant effect on both, inflammation and cognition 17, 18 and the expression level of TREM2 18 .…”

Section: Introductionmentioning

confidence: 99%

Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice

Nam

Mounier

Wolfe

et al. 2017

Sci Rep

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We examined the effect of chronic high fat diet (HFD) on amyloid deposition and cognition of 12-months old APP23 mice, and correlated the phenotype to brain transcriptome and lipidome. HFD significantly increased amyloid plaques and worsened cognitive performance compared to mice on normal diet (ND). RNA-seq results revealed that in HFD mice there was an increased expression of genes related to immune response, such as Trem2 and Tyrobp. We found a significant increase of TREM2 immunoreactivity in the cortex in response to HFD, most pronounced in female mice that correlated to the amyloid pathology. Down-regulated by HFD were genes related to neuron projections and synaptic transmission in agreement to the significantly deteriorated neurite morphology and cognition in these mice. To examine the effect of the diet on the brain lipidome, we performed Shotgun Lipidomics. While there was no difference in the total amounts of phospholipids of each class, we revealed that the levels of 24 lipid sub-species in the brain were significantly modulated by HFD. Network visualization of correlated lipids demonstrated overall imbalance with most prominent effect on cardiolipin molecular sub-species. This integrative approach demonstrates that HFD elicits a complex response at molecular, cellular and system levels in the CNS.

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Lipidomics of Human Brain Aging and Alzheimer's Disease Pathology

Cited by 150 publications

References 193 publications

Specific Metabolomics Adaptations Define a Differential Regional Vulnerability in the Adult Human Cerebral Cortex

Specific Metabolomics Adaptations Define a Differential Regional Vulnerability in the Adult Human Cerebral Cortex

Lipidomics Reveals a Tissue-Specific Fingerprint

Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice

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