Dietary arachidonic acid increases deleterious effects of amyloid-β oligomers on learning abilities and expression of AMPA receptors: putative role of the ACSL4-cPLA balance.

Background: Polyunsaturated fatty acids play a crucial role in neuronal function, and the modification of these compounds in the brain could have an impact on neurodegenerative diseases such as Alzheimer's disease. Despite the fact that arachidonic acid is the second foremost polyunsaturated fatty acid besides docosahexaenoic acid, its role and the regulation of its transfer and mobilization in the brain are poorly known.

Methods: Two groups of 39 adult male BALB/c mice were fed with an arachidonic acid-enriched diet or an oleic acid-enriched diet, respectively, for 12 weeks.

Additional use of Aβ₄₂/Aβ₄₀ ratio with cerebrospinal fluid biomarkers P-tau and Aβ₄₂ increases the level of evidence of Alzheimer's disease pathophysiological process in routine practice.

Background: Cerebrospinal fluid (CSF) biomarkers have recently been included in the criteria for the diagnosis of Alzheimer's disease (AD). Since interpretation of CSF profile requires the combination of three parameters, biological data are not always conclusive and isolated elevation of phosphorylated tau (P-tau) or reduction of amyloid-β (Aβ)42 alone can be observed. In these cases, Aβ42/Aβ40 ratio could be more relevant than Aβ42 absolute values by considering inter-individual variations in the total amyloid load.

Critical role of cPLA2 in Aβ oligomer-induced neurodegeneration and memory deficit.

Soluble beta-amyloid (Aβ) oligomers are considered to putatively play a critical role in the early synapse loss and cognitive impairment observed in Alzheimer's disease. We previously demonstrated that Aβ oligomers activate cytosolic phospholipase A(2) (cPLA(2)), which specifically releases arachidonic acid from membrane phospholipids. We here observed that cPLA(2) gene inactivation prevented the alterations of cognitive abilities and the reduction of hippocampal synaptic markers levels noticed upon a single intracerebroventricular injection of Aβ oligomers in wild type mice.

Up-regulation of hepatic lipolysis stimulated lipoprotein receptor by leptin: a potential lever for controlling lipid clearance during the postprandial phase.

As a hepatic receptor for triglyceride-rich lipoproteins, the lipolysis-stimulated lipoprotein receptor (LSR) may be involved in the dynamics of lipid distribution between the liver and peripheral tissues. Here, we explore the potential role of leptin in regulating LSR. At physiological concentrations (1-10 ng/ml), leptin increased LSR protein and mRNA levels in Hepa1-6 cells through an ERK1/2-dependent and α-amanitin-sensitive pathway.

Ciliary neurotrophic factor cell-based delivery prevents synaptic impairment and improves memory in mouse models of Alzheimer's disease.

The development of novel therapeutic strategies for Alzheimer's disease (AD) represents one of the biggest unmet medical needs today. Application of neurotrophic factors able to modulate neuronal survival and synaptic connectivity is a promising therapeutic approach for AD. We aimed to determine whether the loco-regional delivery of ciliary neurotrophic factor (CNTF) could prevent amyloid-beta (Abeta) oligomer-induced synaptic damages and associated cognitive impairments that typify AD.

The essential role of lipids in Alzheimer's disease.

In the absence of efficient diagnostic and therapeutic tools, Alzheimer's disease (AD) is a major public health concern due to longer life expectancy in the Western countries. Although the precise cause of AD is still unknown, soluble beta-amyloid (Abeta) oligomers are considered the proximate effectors of the synaptic injury and neuronal death occurring in the early stages of AD. Abeta oligomers may directly interact with the synaptic membrane, leading to impairment of synaptic functions and subsequent signalling pathways triggering neurodegeneration.

Docosahexaenoic acid prevents neuronal apoptosis induced by soluble amyloid-beta oligomers.

A growing body of evidence supports the notion that soluble oligomers of amyloid-beta (Abeta) peptide interact with the neuronal plasma membrane, leading to cell injury and inducing death-signalling pathways that could account for the increased neurodegeneration occurring in Alzheimer's disease (AD). Docosahexaenoic acid (DHA, C22:6, n-3) is an essential polyunsaturated fatty acid in the CNS and has been shown in several epidemiological and in vivo studies to have protective effects against AD and cognitive alterations. However, the molecular mechanisms involved remain unknown.