Basic Science and Pathogenesis.

Background: Fundamental questions remain about the key mechanisms that initiate Alzheimer's disease (AD) and the factors that promote its progression. Here we report the successful generation of the first genetically-engineered marmosets that carry knock-in (KI) point mutations in the presenilin-1 (PSEN1) gene that can be studied from birth throughout lifespan.

Method: CRISPR/Cas9 was used to generate marmosets with C410Y or A426P point mutations in PSEN1.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the most common global cause of dementia, with no real cure available. Despite extensive genetic findings from large-scale genetic associations and similar studies, our understanding of AD is largely hindered by its long, asymptomatic progression with limited access to human brain tissue. Animal models like the marmoset allow for longitudinal analysis of disease by enabling the assaying of disease-specific phenotypes that mimic human pathophysiology.

A propensity score-matched comparison between single-stage and multistage anterior/posterior lumbar fusion surgery: a Michigan Spine Surgery Improvement Collaborative study.

Objective: Patients undergoing anterior/posterior lumbar fusion surgery can undergo either a single-stage or multistage operation, depending on surgeon preference. The goal of this study was to assess different patient outcomes between single-stage and multistage lumbar fusion procedures in a multicenter setting.

Methods: The Michigan Spine Surgery Improvement Collaborative database was queried for anterior/posterior lumbar fusion surgeries between July 2018 and January 2022.

Effects of gene dosage on cognitive ability: A function-based association study across brain and non-brain processes.

Copy-number variants (CNVs) that increase the risk for neurodevelopmental disorders also affect cognitive ability. However, such CNVs remain challenging to study due to their scarcity, limiting our understanding of gene-dosage-sensitive biological processes linked to cognitive ability. We performed a genome-wide association study (GWAS) in 258,292 individuals, which identified-for the first time-a duplication at 2q12.