Farlow and colleagues identify genetic variants contributing to disease risk in familial Parkinson disease (PD). They identify genes containing rare, likely deleterious, genetic variants in individuals with familial PD using a 2-stage exome sequencing study design. TNK2 and TNR harbored rare, likely deleterious, variants in individuals having familial PD, with similar findings in an independent cohort. Mathias Toft, MD, PhD, and Owen A. Ross, PhD, provide an editorial.
Eisenmenger and colleagues assess the natural history of the magnetic resonance imaging (MRI) signal abnormalities on diffusion-weighted imaging (DWI) in sporadic Creutzfeldt-Jakob disease (CJD) to improve our understanding of the pathogenesis and to investigate the potential of DWI as a biomarker of disease progression, with histopathological correlation. They correlated regional and total brain scores with disease duration. They report that DWI in the basal ganglia may provide a noninvasive biomarker in future therapeutic trials.
Petersen and coauthors explore the effect of elevated amyloid levels on subsequent changes in cognition and biomarkers. Cognitive measures of memory, language, attention/executive function, visuospatial skills, Pittsburgh Compound B levels, hippocampal and ventricular volumes, and fluorodeoxyglucose positron emission tomography measures were obtained. They find that elevated amyloid levels at baseline were associated with worse cognition and imaging biomarkers at baseline and with greater clinical decline and neurodegeneration in persons selected from a population-based study.
The Huntington Study Group PHAROS Investigators identify the earliest features associated with the motor diagnosis of Huntington disease (HD) in the Prospective Huntington at Risk Observational Study (PHAROS). They compared HD mutation status in individuals with cytosine-adenine-guanine (CAG) expansion vs those without CAG expansion. They conclude that relatively large treatment effects would be required to mount a randomized, placebo-controlled clinical trial involving premanifest HD individuals who carry the CAG expansion.
Highlights. JAMA Neurol. 2016;73(1):5. doi:10.1001/jamaneurol.2015.2431