Plasma miRNAs across the Alzheimer's disease continuum: Relationship to central biomarkers.

Introduction: MicroRNAs (miRNAs) play important roles in gene expression regulation and Alzheimer's disease (AD) pathogenesis.

Methods: We investigated the association between baseline plasma miRNAs and central AD biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 803): amyloid, tau, and neurodegeneration (A/T/N). Differentially expressed miRNAs and their targets were identified, followed by pathway enrichment analysis.

Perinatal choline supplementation prevents learning and memory deficits and reduces brain amyloid Aβ42 deposition in AppNL-G-F Alzheimer's disease model mice.

Alzheimer's disease (AD) is characterized by cognitive and memory impairments and neuropathological abnormalities. AD has no cure, inadequate treatment options, and a limited understanding of possible prevention measures. Previous studies have demonstrated that AD model mice that received a diet high in the essential nutrient choline had reduced amyloidosis, cholinergic deficits, and gliosis, and increased neurogenesis.

A Narrative Review on Maternal Choline Intake and Liver Function of the Fetus and the Infant; Implications for Research, Policy, and Practice.

Dietary choline is needed to maintain normal health, including normal liver function in adults. Fatty liver induced by a choline-deficient diet has been consistently observed in human and animal studies. The effect of insufficient choline intake on hepatic fat accumulation is specific and reversible when choline is added to the diet.

Cerebral Gray and White Matter Monogalactosyl Diglyceride Levels Rise with the Progression of Alzheimer's Disease.

Background: Multiple studies have reported brain lipidomic abnormalities in Alzheimer's disease (AD) that affect glycerophospholipids, sphingolipids, and fatty acids. However, there is no consensus regarding the nature of these abnormalities, and it is unclear if they relate to disease progression.

Objective: Monogalactosyl diglycerides (MGDGs) are a class of lipids which have been recently detected in the human brain.

Is dietary choline intake related to dementia and Alzheimer's disease risks? Results from the Framingham Heart Study.

Background: The positive association of choline for cognition has been reported in both animal and human studies, yet the associations of choline with the risks of incident dementia or Alzheimer's disease (AD) in humans is unclear.

Objectives: Our objective was to test the hypothesis that lower or higher dietary choline intake is associated with increased or decreased, respectively, risks of incident dementia and AD.

Methods: Data from the Framingham Heart Study Offspring Cohort exam 5 to exam 9 were used.

Accelerated Breakdown of Phosphatidylcholine and Phosphatidylethanolamine Is a Predominant Brain Metabolic Defect in Alzheimer's Disease.

Numerous studies have demonstrated defects in multiple metabolic pathways in Alzheimer's disease (AD), detected in autopsy brains and in the cerebrospinal fluid in vivo. However, until the advent of techniques capable of measuring thousands of metabolites in a single sample, it has not been possible to rank the relative magnitude of these abnormalities. A recent study provides evidence that the abnormal turnover of the brain's most abundant phospholipids: phosphatidylcholine and phosphatidylethanolamine, constitutes a major metabolic pathology in AD.

Monomeric C-reactive protein via endothelial CD31 for neurovascular inflammation in an ApoE genotype-dependent pattern: A risk factor for Alzheimer's disease?

In chronic peripheral inflammation, endothelia in brain capillary beds could play a role for the apolipoprotein E4 (ApoE4)-mediated risk for Alzheimer's disease (AD) risk. Using human brain tissues, here we demonstrate that the interactions of endothelial CD31 with monomeric C-reactive protein (mCRP) versus ApoE were linked with shortened neurovasculature for AD pathology and cognition. Using ApoE knock-in mice, we discovered that intraperitoneal injection of mCRP, via binding to CD31 on endothelial surface and increased CD31 phosphorylation (pCD31), leading to cerebrovascular damage and the extravasation of T lymphocytes into the ApoE4 brain.

MicroRNAs as Candidate Biomarkers for Alzheimer's Disease.

The neurological damage of Alzheimer's disease (AD) is thought to be irreversible upon onset of dementia-like symptoms, as it takes years to decades for occult pathologic changes to become symptomatic. It is thus necessary to identify individuals at risk for the development of the disease before symptoms manifest in order to provide early intervention. Surrogate markers are critical for early disease detection, stratification of patients in clinical trials, prediction of disease progression, evaluation of response to treatment, and also insight into pathomechanisms.

The Expression of Activin Receptor-Like Kinase 1 (ACVRL1/ALK1) in Hippocampal Arterioles Declines During Progression of Alzheimer's Disease.

Cerebral amyloid angiopathy (CAA) in Alzheimer's disease (AD)-deposition of beta amyloid (Aβ) within the walls of cerebral blood vessels-typically accompanies Aβ buildup in brain parenchyma and causes abnormalities in vessel structure and function. We recently demonstrated that the immunoreactivity of activin receptor-like kinase 1 (ALK1), the type I receptor for circulating BMP9/BMP10 (bone morphogenetic protein) signaling proteins, is reduced in advanced, but not early stages of AD in CA3 pyramidal neurons. Here we characterize vascular expression of ALK1 in the context of progressive AD pathology accompanied by amyloid angiopathy in postmortem hippocampi using immunohistochemical methods.

Choline: The Neurocognitive Essential Nutrient of Interest to Obstetricians and Gynecologists.

Choline is an essential nutrient for proper liver, muscle, and brain functions as well as for lipid metabolism and cellular membrane composition and repair. Humans can produce small amounts of choline via the hepatic phosphatidylethanolamine -methyltransferase pathway; however, most individuals must consume this vitamin through the diet to prevent deficiency. An individual's dietary requirement for choline is dependent on common genetic variants in genes required for choline, folate, and one-carbon metabolism.

Choline: The Underconsumed and Underappreciated Essential Nutrient.

Choline has been recognized as an essential nutrient by the Food and Nutrition Board of the National Academies of Medicine since 1998. Its metabolites have structural, metabolic, and regulatory roles within the body. Humans can endogenously produce small amounts of choline via the hepatic phosphatidylethanolamine -methyltransferase pathway.

Methionine Sulfoxide Reductase-B3 Risk Allele Implicated in Alzheimer's Disease Associates with Increased Odds for Brain Infarcts.

Genome-wide association studies identified a single nucleotide polymorphism (SNP) in the MSRB3 gene encoding Methionine Sulfoxide Reductase-B3 (MsrB3) to be associated with the risk for low hippocampal volume and late onset Alzheimer's disease (AD). Subsequently, we identified AD-associated abnormal patterns of neuronal and vascular MsrB3 expression in postmortem hippocampi. The present study investigated the relationship between the MSRB3 SNP rs61921502, G (minor/risk allele) and MRI measures of brain injury including total brain volume, hippocampal volume, and white matter hyperintensities using linear regression models; the presence of brain infarcts using logistic regression models; and the incidence of stroke, dementia, and AD using Cox proportional hazards models in 2,038 Framingham Heart Study Offspring participants with MRI administered close to examination cycle 7 (1998-2001).

Immunohistochemical Analysis of Activin Receptor-Like Kinase 1 (ACVRL1/ALK1) Expression in the Rat and Human Hippocampus: Decline in CA3 During Progression of Alzheimer's Disease.

The pathophysiology of Alzheimer's disease (AD) includes signaling defects mediated by the transforming growth factor β-bone morphogenetic protein-growth and differentiation factor (TGFβ-BMP-GDF) family of proteins. In animal models of AD, administration of BMP9/GDF2 improves memory and reduces amyloidosis. The best characterized type I receptor of BMP9 is ALK1.

Protective effects of 7,8-dihydroxyflavone on neuropathological and neurochemical changes in a mouse model of Alzheimer's disease.

Interest in brain-derived neurotrophic factor (BDNF) was greatly enhanced when it was recognized that its expression is reduced in neurodegenerative disorders, especially in Alzheimer's disease (AD). BDNF signaling through the TrkB receptor has a central role in promoting synaptic transmission, synaptogenesis, and facilitating synaptic plasticity making the BDNF-TrkB signaling pathway an attractive candidate for targeted therapies. Here we investigated the early effect of the small molecule TrkB agonist, 7,8 dihydroxyflavone (7,8-DHF), on AD-related pathology, dendritic arborization, synaptic density, and neurochemical changes in the 5xFAD mouse model of AD.

Pramlintide: The Effects of a Single Drug Injection on Blood Phosphatidylcholine Profile for Alzheimer's Disease.

Studies suggest that a single injection of pramlintide, an amylin analog, induces changes in Alzheimer's disease (AD) biomarkers in the blood of AD mouse models and AD patients. The aim of this study was to examine whether a pramlintide challenge combined with a phosphatidylcholine (PC) profile diagnoses of AD and mild cognitive impairment (MCI) better than PC alone. Non-diabetic subjects with cognitive status were administered a single subcutaneous injection of 60 mcg of pramlintide under fasting condition.

Anxiety, neuroinflammation, cholinergic and GABAergic abnormalities are early markers of Gulf War illness in a mouse model of the disease.

Gulf War Illness (GWI) is a chronic disease that affects the 1991 Gulf War (GW) veterans for which treatment is lacking. It has been hypothesized that drugs used to protect military personnel from chemical attacks and insects during the war: pyridostigmine bromide (PB),N, N-diethyl-m-toluamide (DEET), and permethrin (PER) together with stress may have contributed collectively and synergistically to generate GWI. There is a need to find markers of pathology to be used in pre-clinical trials.

Neuroprotective Actions of Dietary Choline.

Choline is an essential nutrient for humans. It is a precursor of membrane phospholipids (e.g.

Methionine Sulfoxide Reductase-B3 (MsrB3) Protein Associates with Synaptic Vesicles and its Expression Changes in the Hippocampi of Alzheimer's Disease Patients.

Genome-wide association studies (GWAS) identified susceptibility loci associated with decreased hippocampal volume, and found hippocampal subfield-specific effects at MSRB3 (methionine sulfoxide reductase-B3). The MSRB3 locus was also linked to increased risk for late onset Alzheimer's disease (AD). In this study, we uncovered novel sites of MsrB3 expression in CA pyramidal layer and arteriolar walls by using automated immunohistochemistry on hippocampal sections from 23 individuals accompanied by neuropathology reports and clinical dementia rating scores.

Correction: Perinatal Choline Supplementation Reduces Amyloidosis and Increases Choline Acetyltransferase Expression in the Hippocampus of the APPswePS1dE9 Alzheimer's Disease Model Mice.

[This corrects the article DOI: 10.1371/journal.pone.

Perinatal Choline Supplementation Reduces Amyloidosis and Increases Choline Acetyltransferase Expression in the Hippocampus of the APPswePS1dE9 Alzheimer's Disease Model Mice.

Prevention of Alzheimer's disease (AD) is a major goal of biomedical sciences. In previous studies we showed that high intake of the essential nutrient, choline, during gestation prevented age-related memory decline in a rat model. In this study we investigated the effects of a similar treatment on AD-related phenotypes in a mouse model of AD.

Amylin Treatment Reduces Neuroinflammation and Ameliorates Abnormal Patterns of Gene Expression in the Cerebral Cortex of an Alzheimer's Disease Mouse Model.

Our recent study has demonstrated that peripheral amylin treatment reduces the amyloid pathology in the brain of Alzheimer's disease (AD) mouse models, and improves their learning and memory. We hypothesized that the beneficial effects of amylin for AD was beyond reducing the amyloids in the brain, and have now directly tested the actions of amylin on other aspects of AD pathogenesis, especially neuroinflammation. A 10-week course of peripheral amylin treatment significantly reduced levels of cerebral inflammation markers, Cd68 and Iba1, in amyloid precursor protein (APP) transgenic mice.

Comment on "Multiple repressive mechanisms in the hippocampus during memory formation".

Cho et al. (Reports, 2 October 2015, p. 82) report that gene repression after contextual fear conditioning regulates hippocampal memory formation.

Intrinsic Cholinergic Neurons in the Hippocampus: Fact or Artifact?

It is generally agreed that hippocampal acetylcholine (ACh) is synthesized and released exclusively from the terminals of the long-axon afferents whose cell bodies reside in the medial septum and diagonal band. The search for intrinsic cholinergic neurons in the hippocampus has a long history; however evidence for the existence of these neurons has been inconsistent, with most investigators failing to detect them using in situ hybridization or immunohistochemical staining of the cholinergic markers, choline acetyltransferase (ChAT) or vesicular acetylcholine transporter (VAChT). Advances in the use of bacterial artificial chromosome (BAC) transgenic mice expressing a reporter protein under the control of the genomic elements of the Chat gene (Chat-BAC mice) have facilitated studies of cholinergic neurons.