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      Selective brain regional changes in lipid profile with human aging

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          Abstract

          Fatty acids are key components in the structural diversity of lipids and play a strategic role in the functional properties of lipids which determine the integrity of neuronal and glial cell membranes, the generation of lipid signaling mediators, and the chemical reactivity of acyl chains. The present study analyzes using gas chromatography the fatty acid profiles of 13 regions of the human central nervous system in healthy individuals ranging from 40 to 80 years old. The outcomes suggest the existence of general traits in fatty acid composition such as an average chain length of 18 carbon atoms, high monounsaturated fatty acid content, and predominance in polyunsaturated fatty acids of those of series n-6 over series n-3 which are shared by all brain regions regardless of age. Our results also show a general sustained and relatively well-preserved lipid profile throughout the adult lifespan in most studied regions (olive, upper vermis, substantia nigra, thalamus, hippocampus, putamen, caudate, occipital cortex, parietal cortex, entorhinal cortex, and frontal cortex) with minor changes that are region-dependent. In contrast, of particular relevance is the involvement of the inferior temporal cortex and cingulate cortex. It is proposed that during normal human brain aging, the lipid profile is resistant to changes with age in most human brain regions to ensure cell survival and function, but some particular regions involved in specific memory domains are greatly affected.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s11357-022-00527-1.

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          Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years.

          Two thousand three hundred and thirty two nonselected brains from 1- to 100-year-old individuals were examined using immunocytochemistry (AT8) and Gallyas silver staining for abnormal tau; immunocytochemistry (4G8) and Campbell-Switzer staining were used for the detection ofβ-amyloid. A total of 342 cases was negative in the Gallyas stain but when restaged for AT8 only 10 were immunonegative. Fifty-eight cases had subcortical tau predominantly in the locus coeruleus, but there was no abnormal cortical tau (subcortical Stages a-c). Cortical involvement (abnormal tau in neurites) was identified first in the transentorhinal region (Stage 1a, 38 cases). Transentorhinal pyramidal cells displayed pretangle material (Stage 1b, 236 cases). Pretangles gradually became argyrophilic neurofibrillary tangles (NFTs) that progressed in parallel with NFT Stages I to VI. Pretangles restricted to subcortical sites were seen chiefly at younger ages. Of the total cases, 1,031 (44.2%) had β-amyloid plaques. The first plaques occurred in the neocortex after the onset of tauopathy in the brainstem. Plaques generally developed in the 40s in 4% of all cases, culminating in their tenth decade (75%). β-amyloid plaques and NFTs were significantly correlated (p < 0.0001). These data suggest that tauopathy associated with sporadic Alzheimer disease may begin earlier than previously thought and possibly in the lower brainstem rather than in the transentorhinal region.
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            REST and Stress Resistance in Aging and Alzheimer’s Disease

            Summary Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during aging are unknown. Here we show that induction of the repressor element 1-silencing transcription/neuron-restrictive silencer factor (REST/NRSF) is a universal feature of normal aging in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Chromatin immunoprecipitation with deep sequencing (ChIP-seq) and expression analysis show that REST represses genes that promote cell death and AD pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein (Aβ) toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional ortholog of REST, C. elegans SPR-4, also protects against oxidative stress and Aβ toxicity. During normal aging, REST is induced in part by cell non-autonomous Wnt signaling. However, in AD, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathologic misfolded proteins. Finally, REST levels during aging are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the aging brain.
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              A neuroscientist's guide to lipidomics.

              Nerve cells mould the lipid fabric of their membranes to ease vesicle fusion, regulate ion fluxes and create specialized microenvironments that contribute to cellular communication. The chemical diversity of membrane lipids controls protein traffic, facilitates recognition between cells and leads to the production of hundreds of molecules that carry information both within and across cells. With so many roles, it is no wonder that lipids make up half of the human brain in dry weight. The objective of neural lipidomics is to understand how these molecules work together; this difficult task will greatly benefit from technical advances that might enable the testing of emerging hypotheses.
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                Author and article information

                Contributors
                nataliamotamartorell@gmail.com
                pol.andres.benito@gmail.com
                meritxell.martin@udl.cat
                jgalolic25@gmail.com
                solcullere@gmail.com
                anna.fernandez@udl.cat
                manuel.portero@udl.cat
                8082ifa@gmail.com
                mariona.jove@udl.cat
                reinald.pamplona@udl.cat
                Journal
                GeroScience
                Geroscience
                GeroScience
                Springer International Publishing (Cham )
                2509-2715
                2509-2723
                11 February 2022
                11 February 2022
                April 2022
                : 44
                : 2
                : 763-783
                Affiliations
                [1 ]GRID grid.15043.33, ISNI 0000 0001 2163 1432, Department of Experimental Medicine, , University of Lleida—Lleida Biomedical Research Institute (UdL-IRBLleida), ; 25198 Lleida, Spain
                [2 ]GRID grid.413448.e, ISNI 0000 0000 9314 1427, Center for Biomedical Research On Neurodegenerative Diseases (CIBERNED), , Institute of Health Carlos III, ; 28220 Madrid, Spain
                [3 ]GRID grid.5841.8, ISNI 0000 0004 1937 0247, Department of Pathology and Experimental Therapeutics, , University of Barcelona, ; L’Hospitalet de Llobregat, 08907 Barcelona, Spain
                [4 ]Institute of Biomedical Research of Bellvitge (IDIBELL), 08907 Hospitalet de Llobregat, Spain
                Author information
                http://orcid.org/0000-0003-4337-6107
                Article
                527
                10.1007/s11357-022-00527-1
                9135931
                35149960
                6137c09c-2dac-48ee-8cf5-12e9342d96ce
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 10 September 2021
                : 29 January 2022
                Funding
                Funded by: Universitat de Lleida
                Categories
                Original Article
                Custom metadata
                © The Author(s), under exclusive licence to American Aging Association 2022

                average chain length,cerebral cortex,human brain regions,fatty acid profile,peroxidizability index,polyunsaturated fatty acids

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