Liu and colleagues analyze purified neurons derived from human induced pluripotent stem cells from patients carrying 3 different presenilin 1 mutations and nondemented control individuals in the absence of any overexpression. Adult human skin biopsies were obtained from volunteers at the Alzheimer Disease Research Center, University of California, San Diego. The results suggest that biomarker signatures obtained with such models are misleading and that human neurons derived from human induced pluripotent stem cells provide a unique signature that will more accurately reflect drug response in human patients and in cerebrospinal fluid biomarker changes observed during γ-secretase modulator treatment. Editorial perspective is provided by Fan Liao, PhD, and David M. Holtzman, MD.
Continuing Medical Education
Gardner and coauthors quantify the risk of dementia among adults with recent traumatic brain injury (TBI) compared with adults with non-TBI trauma (NTT). All patients 55 years or older diagnosed as having TBI or NTT in 2005 and 2006 and who did not have baseline dementia or die during hospitalization (n = 164 661) were identified in a California statewide administrative health database of emergency department (ED) and inpatient visits. Among patients evaluated in the ED or inpatient settings, those with moderate to severe TBI at 55 years or older or mild TBI at 65 years or older had an increased risk of developing dementia. Editorial perspective is provided by Steven T. DeKosky, MD.
Langer-Gould and colleagues determine whether vaccines, particularly those for hepatitis B and human papillomavirus, increase the risk of multiple sclerosis (MS) or other central nervous system demyelinating syndromes (CNS ADS). A nested case-control study was conducted using data obtained from the complete electronic health records of Kaiser Permanente Southern California members. They found no longer-term association of vaccines with MS or any other CNS ADS, which argues against a causal association.
Russell and coauthors evaluate whether [18F]MNI-659 (2-(2-(3-(4-(2-[18F]fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione), a novel phosphodiesterase 10 positron emission tomography (PET) ligand, is a sensitive marker for striatal changes in early Huntington disease (HD). A cohort of individuals with HD, including premanifest (pre-HD) or manifest with motor signs (mHD), underwent clinical assessments, genetic determination, [18F]MNI-659 PET imaging, and brain magnetic resonance imaging. As a promising striatal imaging biomarker, [18F]MNI-659 is potentially capable of assessing the extent of disease in early mHD.
Kantarci et al investigate the effects of Alzheimer disease–related gray matter neurodegeneration and high β-amyloid on white matter microstructure in older adults without dementia. Participants included in the Mayo Clinic Study of Aging (N = 701) who underwent magnetic resonance imaging, diffusion tensor imaging (DTI), and positron emission tomography studies with diagnoses of cognitively normal (n = 570) or mild cognitive impairment (n = 131) were included. A high amyloid load does not influence DTI-based measures of white matter integrity in the absence of coexistent gray matter neurodegeneration in older adults without dementia.
Highlights. JAMA Neurol. 2014;71(12):1467. doi:10.1001/jamaneurol.2013.4181