Lipidomics research could provide insights of pathobiological mechanisms in Alzheimer’s disease. This study explores a battery of plasma lipids that can differentiate Alzheimer’s disease (AD) patients from healthy controls and determines whether lipid profiles correlate with genetic risk for AD. AD plasma samples were collected from the Sydney Memory and Ageing Study (MAS) Sydney, Australia (aged range 75–97 years; 51.2% male). Untargeted lipidomics analysis was performed by liquid chromatography coupled–mass spectrometry (LC–MS/MS). We found that several lipid species from nine lipid classes, particularly sphingomyelins (SMs), cholesterol esters (ChEs), phosphatidylcholines (PCs), phosphatidylethanolamines (PIs), phosphatidylinositols (PIs), and triglycerides (TGs) are dysregulated in AD patients and may help discriminate them from healthy controls. However, when the lipid species were grouped together into lipid subgroups, only the DG group was significantly higher in AD. ChEs, SMs, and TGs resulted in good classification accuracy using the Glmnet algorithm (elastic net penalization for the generalized linear model [glm]) with more than 80% AUC. In general, group lipids and the lipid subclasses LPC and PE had less classification accuracy compared to the other subclasses. We also found significant increases in SMs, PIs, and the LPE/PE ratio in human U251 astroglioma cell lines exposed to pathophysiological concentrations of oligomeric Aβ42. This suggests that oligomeric Aβ42 plays a contributory, if not causal role, in mediating changes in lipid profiles in AD that can be detected in the periphery. In addition, we evaluated the association of plasma lipid profiles with AD-related single nucleotide polymorphisms (SNPs) and polygenic risk scores (PRS) of AD. We found that FERMT2 and MS4A6A showed a significantly differential association with lipids in all lipid classes across disease and control groups. ABCA7 had a differential association with more than half of the DG lipids (52.63%) and PI lipids (57.14%), respectively. Additionally, 43.4% of lipids in the SM class were differentially associated with CLU. More than 30% of lipids in ChE, PE, and TG classes had differential associations with separate genes (ChE-PICALM, SLC24A4, and SORL1; PE-CLU and CR1; TG-BINI) between AD and control group. These data may provide renewed insights into the pathobiology of AD and the feasibility of identifying individuals with greater AD risk.

Zero valent iron core–iron oxide shell nanoparticles coated with a multi-phosphonate brush co-polymer are shown to be small and effective magnetic nanoparticle imaging tracers.

Aim: Quantum dots (QDs) are nanoparticles that have an emerging application as theranostic agents in several neurodegenerative diseases. The advantage of QDs as nanomedicine is due to their unique optical properties that provide high sensitivity, stability and selectivity at a nanoscale range. Objective: To offer renewed insight into current QD research and elucidate its promising application in Alzheimer's disease (AD) diagnosis and therapy. Methods: A comprehensive literature search was conducted in PubMed and Google Scholar databases that included the following search terms: ‘quantum dots’, ‘blood–brain barrier’, ‘cytotoxicity’, ‘toxicity’ and ‘Alzheimer's disease’; PRISMA guidelines were adhered to. Results: Thirty-four publications were selected to evaluate the ability of QDs to cross the blood–brain barrier, potential toxicity and current AD diagnostic and therapeutic applications. Conclusion: QD's unique optical properties and versatility to conjugate to various biomolecules, while maintaining a nanoscale size, render them a promising theranostic tool in AD.

Nanoparticle (NP)-based magnetic contrast agents have opened the potential for MRI to be used for early diagnosis of Alzheimer’s disease (AD). This article aims to review the current progress of research in this field. A comprehensive literature search was performed based on PubMed, Medline, EMBASE, PsychINFO and Scopus databases using the following terms: ‘Alzheimer’s disease’ AND ‘nanoparticles’ AND ‘Magnetic Resonance Imaging.’ 33 studies were included that described the development and utility of various NPs for AD imaging, including their coating, functionalization, MRI relaxivity, toxicity and bioavailability. NPs show immense promise for neuroimaging, due to superior relaxivity and biocompatibility compared with currently available imaging agents. Consistent reporting is imperative for further progress in this field.

In the absence of national standards for scholarly requirements, paediatric resident training varies significantly across Canadian programs. This variability may contribute to significant differences in trainee experiences and productivity. A panel of coordinators of paediatric resident research programs from across Canada met in 2014, to share experiences and identify barriers to successful resident scholarly activity. A survey of all programs was completed in 2015. A scoping review and series of meetings led to the development of a proposed list of expectations, timelines for successful completion and consequences for not completing a scholarly project. We propose a harmonized list of scholarly competencies and activities for paediatric residents in Canada to accomplish before completing their training. We also propose that programs implement standardized timelines and consequences in the event that a resident does not meet their program's scholarly expectations.

Background Nanoparticle‐based magnetic contrast agents have opened the potential for Magnetic Resonance Imaging (MRI) to be used for early non‐invasive diagnosis of Alzheimer’s disease (AD). Current methods for clinical diagnosis in the early stages of the disease, such as Positron Emission Tomography imaging of amyloid build‐up, are limited by their availability and cost. The aim of this research is to develop a novel non‐toxic amyloid targeted nanoparticle which can successfully permeate the blood brain barrier and bind amyloid plaques resulting in enhanced contrast in the MR image and improved diagnostic sensitivity. Methods Targeted iron nanoparticles were assessed using a U‐251 cell line to determine their in vitro toxicity. Transmission electron microscopy was used to determine the movement of the nanoparticles within the cell and in vitro binding to amyloid fibrils. APPSwe/PSEN1 mice were treated with increasing doses of targeted and non‐targeted nanoparticles to evaluate acute in vivo toxicity, in addition to nanoparticle biodistribution and MRI contrast enhancement. Results The novel targeted nanoparticles have demonstrated no significant in vitro toxicity and electron microscopy results show their movement through the endocytic cycle within the cell, demonstrating an effective degradation and clearance pathway (Figure). No acute toxicity was observed in the animal model. In addition, immunohistochemistry demonstrated nanoparticles to co‐localise with plaques on ex vivo brain sections. Conclusion The present work shows promising preliminary results in the development of a targeted non‐invasive method of early AD diagnosis using contrast enhanced MRI.