Brain-derived extracellular vesicle microRNAs in Lewy body and Alzheimer's disease.

Introduction: Robust plasma-based biomarkers to distinguish Lewy body disease (LBD) and Alzheimer's disease (AD) are currently lacking. We applied track-etch magnetic nanopore (TENPO) sorting for enrichment of brain-derived extracellular vesicle (EV) signatures as potential biomarkers to address this gap.

Methods: We analyzed plasma from 137 autopsy-confirmed patients [30 LBD, 31 AD, 30 AD/LBD, 19 AD with amygdala Lewy bodies (AD/ALB), and 27 controls], sequencing miRNAs from TENPO-isolated GluR2-positive (neuron-enriched) and GLAST-positive (astrocyte-enriched) EVs, and measuring plasma proteins (Aβ40, Aβ42, tau, p-Tau181, p-Tau231) via SIMOA.

Supporting the Deceased, Their Families, and Their Communities Part 1: Why Establish an Office of Decedent Affairs.

Context.—: Decedent Affairs Offices and Programs can serve as an avenue to assist medical centers in facilitating efficient and comprehensive decedent management, despite a paucity of literature on their roles, establishment, and efficacy.

Objective.

Supporting the Deceased, Their Families, and Their Communities Part 2: Practical Guidance for Building an Office of Decedent Affairs.

Context.—: After-death care can be complicated and time-consuming for clinical staff, and frustrating for bereaved families. Delays and errors can have damaging legal and reputational consequences for hospitals.

Methylome analysis of FTLD patients with TDP-43 pathology identifies epigenetic signatures specific to pathological subtypes.

Background: In the last decade, the importance of DNA methylation in the functioning of the central nervous system has been highlighted through associations between methylation changes and differential expression of key genes involved in aging and neurodegenerative diseases. In frontotemporal lobar degeneration (FTLD), aberrant methylation has been reported in causal disease genes including GRN and C9orf72; however, the genome-wide contribution of epigenetic changes to the development of FTLD remains largely unexplored.

Methods: We performed reduced representation bisulfite sequencing of matched pairs of post-mortem tissue from frontal cortex (FCX) and cerebellum (CER) from pathologically confirmed FTLD patients with TDP-43 pathology (FTLD-TDP) further divided into five subtypes and including both sporadic and genetic forms (N = 25 pairs per group), and neuropathologically normal controls (N = 42 pairs).

An FDG-PET-Based Machine Learning Framework to Support Neurologic Decision-Making in Alzheimer Disease and Related Disorders.

Background And Objectives: Distinguishing neurodegenerative diseases is a challenging task requiring neurologic expertise. Clinical decision support systems (CDSSs) powered by machine learning (ML) and artificial intelligence can assist with complex diagnostic tasks by augmenting user capabilities, but workflow integration poses many challenges. We propose that a modeling framework based on fluorodeoxyglucose PET (FDG-PET) imaging can address these challenges and form the basis of an effective CDSS for neurodegenerative disease.