The Lipids Issue

Cell Tissue Res. 2016 Jul 23. [Epub ahead of print]
Mitochondrial lipids in neurodegeneration.
Aufschnaiter A1, Kohler V1, Diessl J2, Peselj C2, Carmona-Gutierrez D1, Keller W1, Büttner S3,4.
Author information
Mitochondrial dysfunction is a common feature of many neurodegenerative diseases, including proteinopathies such as Alzheimer’s or Parkinson’s disease, which are characterized by the deposition of aggregated proteins in the form of insoluble fibrils or plaques. The distinct molecular processes that eventually result in mitochondrial dysfunction during neurodegeneration are well studied but still not fully understood. However, defects in mitochondrial fission and fusion, mitophagy, oxidative phosphorylation and mitochondrial bioenergetics have been linked to cellular demise. These processes are influenced by the lipid environment within mitochondrial membranes as, besides membrane structure and curvature, recruitment and activity of different proteins also largely depend on the respective lipid composition. Hence, the interaction of neurotoxic proteins with certain lipids and the modification of lipid composition in different cell compartments, in particular mitochondria, decisively impact cell death associated with neurodegeneration. Here, we discuss the relevance of mitochondrial lipids in the pathological alterations that result in neuronal demise, focussing on proteinopathies.
Lipids; Mitochondria; Mitochondria-associated membranes; Mitochondrial dynamics; Neurodegeneration
PMID: 27449929 DOI: 10.1007/s00441-016-2463-1

Perspect Infirm. 2016 Jan-Feb;13(1):66-7.
[Alzheimer disease. Fat droplets in the brain: new avenues for research].
[Article in French]
[No authors listed]
Comment on
Aberrant Lipid Metabolism in the Forebrain Niche Suppresses Adult Neural Stem Cell Proliferation in an Animal Model of Alzheimer’s Disease. [Cell Stem Cell. 2015]
PMID: 26998544

Alzheimers Dement. 2016 Sep 28. pii: S1552-5260(16)30022-X. doi: 10.1016/j.jalz.2016.08.003. [Epub ahead of print]
Association of blood lipids with Alzheimer’s disease: A comprehensive lipidomics analysis.
Proitsi P1, Kim M2, Whiley L2, Simmons A3, Sattlecker M3, Velayudhan L4, Lupton MK5, Soininen H6, Kloszewska I7, Mecocci P8, Tsolaki M9, Vellas B10, Lovestone S11, Powell JF4, Dobson RJ12, Legido-Quigley C2.
Author information
The aim of this study was to (1) replicate previous associations between six blood lipids and Alzheimer’s disease (AD) (Proitsi et al 2015) and (2) identify novel associations between lipids, clinical AD diagnosis, disease progression and brain atrophy (left/right hippocampus/entorhinal cortex).
We performed untargeted lipidomic analysis on 148 AD and 152 elderly control plasma samples and used univariate and multivariate analysis methods.
We replicated our previous lipids associations and reported novel associations between lipids molecules and all phenotypes. A combination of 24 molecules classified AD patients with >70% accuracy in a test and a validation data set, and we identified lipid signatures that predicted disease progression (R2 = 0.10, test data set) and brain atrophy (R2 ≥ 0.14, all test data sets except left entorhinal cortex). We putatively identified a number of metabolic features including cholesteryl esters/triglycerides and phosphatidylcholines.
Blood lipids are promising AD biomarkers that may lead to new treatment strategies.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Alzheimer’s disease; Biomarkers; Brain atrophy; Classification; Dementia; Lipidomics; Machine learning; Metabolomics; Multivariate; Random forest; Rate of cognitive decline; sMRI
PMID: 27693183 DOI: 10.1016/j.jalz.2016.08.003

Curr Med Chem. 2016 Nov 22. [Epub ahead of print]
Lipids at the Cross-road of Autoimmunity in Multiple Sclerosis.
Reale M1, Sánchez-Ramón S2.
Author information
Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by demyelination and neurodegeneration, driven by a Th17/Th1-immune response, which afflicts mainly young women. Although MS causes are not completely known, it is notorious that the disease is characterized by an extended focal degradation of the myelin sheath, with ulterior axon and neuronal damage. Lipid molecules play a main dual role in MS, both as target molecules of myelin destruction and as mediators of inflammation. Indeed, recent cumulative evidence suggests that abnormalities in the lipid-binding proteins of myelin and sphingolipid content that confer increased immunogenicity may underlie the autoimmune response against the myelin sheath. CNS is after all, the second organ richer on lipid content after adipose tissue. On the other hand, soluble factors called adipokines, secreted by adipose tissue, modulate inflammatory responses and contribute to metabolic dysfunction, which may be important in MS pathophysiology. Disability accumulation in MS patients is slow but persistent, often leading to a decreased mobility and physical activity, resulting in more weakness, fatigue and associated increased risk of the metabolic syndrome (MetS). In turn, MetS may trigger MS in susceptible individuals and is a worse prognostic factor. Here we review what are the facts linking lipids, MetS and MS, what we do not know yet, and what we should do to move this field forward.
PMID: 27881065

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