Beclin 1 is a protein involved in the regulation of autophagy that has been shown to be reduced in patients with Alzheimer disease. Jaeger and Wyss-CorayArticle summarize the current research data that link disturbances in autophagy, a cellular degradation and maintenance pathway, to the development of Alzheimer disease and related neurodegenerative diseases. It also provides a brief overview of the existing pharmacological interventions available to modulate autophagy activity in mammalian cells.
Karussis and colleaguesArticle evaluate the feasibility, safety, and immunological effects of intrathecal and intravenous administration of autologous mesenchymal stromal cells in patients with multiple sclerosis and amyotrophic lateral sclerosis. They report that mesenchymal stromal cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis is a clinically feasible and relatively safe procedure that induces immediate immunomodulatory effects.
Rundek et alArticle determine the association between insulin resistance and risk of first ischemic stroke in a large, multiethnic, stroke-free cohort without diagnosis of diabetes. They find that insulin resistance, estimated by the homeostatic model assessment, is a marker of increased risk of incident stroke among nondiabetic individuals. Their findings emphasize the need to better characterize individuals at increased risk of stroke and the potential role of primary preventive therapies targeted at insulin resistance. Editorial perspective is provided by Graeme J. Hankey,
MD, FRCP, FRCP(Edin), FRACP, and Tan Ze Feng, MD.Article
Kalluri and colleaguesArticle have developed a novel bioassay for quantification and characterization of human anti–aquaporin 4 (AQP4) antibodies based on high-level expression of native AQP4 protein on the surface of human astroglioma cells. In neuromyelitis optica, this assay may help to unravel the biological function of anti–native AQP4 IgG. Their findings demonstrate the potential of bioassays to characterize biologically relevant antibodies in human autoimmune diseases.
Albright et alArticle have determined population access to certified primary stroke centers (PSCs) in the United States using the current ground ambulance system and how emergency medical services policy changes such as crossing state lines and using prehospital air ambulance transport could affect population access to stroke care. They show that about half of the US population has timely access to a primary stroke center. Using air ambulances to triage patients with ischemic stroke to a primary stroke center would increase the percentage of the US population having prompt access to stroke care. Their data have implications for the ongoing design of the US stroke system.
Denier and colleaguesArticle have determined the prevalence and determinants of early-onset stroke (ES) in a prospective cohort of consecutive patients with magnetic resonance imaging–confirmed cerebral infarction. Cortical hemispheric location of ischemic strokes is associated with a higher risk of ES. Among these cases, the watershed mechanism is a strong and independent determinant of stroke-related ES.
Baker et alArticle have determined whether certain retinal microvascular signs are associated with lobar intracerebral hemorrhage (ICH) to improve understanding of its underlying cerebral vasculopathy. Patients with lobar ICH were more likely than patients with lacunar or nonlacunar cerebral infarction to have retinopathy lesions, suggesting breakdown of the blood-retina barrier in patients with lobar ICH. Their findings support a distinct vasculopathy in lobar ICH compared with other acute stroke subtypes resulting from cerebral small vessel disease or ischemic infarction.
He and colleaguesArticle have investigated associations between magnetic resonance imaging brain morphology, cerebrovascular risk clinical diagnosis, and cognition among older persons living in urban Shanghai. Magnetic resonance imaging brain morphology changes were significantly associated with clinical diagnosis. In addition, blood pressure was highly associated with cerebrovascular risk score and white matter hyperintensities. These results suggest that magnetic resonance imaging is a valuable measure of brain injury in a Chinese cohort and can serve to assess the effects of various degenerative and cerebrovascular pathologies.
Normalized brain volume (BV) measures in participants with normal cognition (NC) and in patients with amnestic mild cognitive impairment (aMCI) and dementia. HV indicates hippocampal volume; WMH, white matter hyperintensity.
Geser et alArticle note that major psychiatric diseases such as schizophrenia and mood disorders have not been linked to a specific pathology, but their clinical features overlap with some aspects of the behavioral variant of frontotemporal lobar degeneration. Although the significance of pathological 43-kDa (transactivation response) DNA-binding protein (TDP-43) for frontotemporal lobar degeneration was appreciated only recently, the prevalence of TDP-43 pathology in severe mental illness vs controls has not been systematically addressed. We therefore examined patients with chronic psychiatric diseases, mainly schizophrenia, for evidence of neurodegenerative TDP-43 pathology compared with controls. The similar findings of TDP-43 pathology in elderly patients with severe mental illness and controls suggest common age-dependent TDP-43 changes in limbic brain areas that may signify that these regions are affected early in the course of a cerebral TDP-43 multisystem proteinopathy.
Stratigopoulos and colleaguesArticle have investigated the potential association of plastin 3 (PLS3) expression levels in blood with disease severity. In postpubertal female patients, PLS3 expression was greatest in those with type III spinal muscular atrophy, intermediate in patients with type II, and lowest in patients with type I. Expression of PLS3 correlated with SMN2 copy number and the gross motor function measure only in postpubertal female patients.
Sato et alArticle have mapped the disease locus to identify a gene mutation in a Japanese family with autosomal dominant cerebellar ataxia. They describe a dominant cerebellar ataxia mapping to 5q31-q33.1 but with neither CAG repeat expansion nor other mutations of the PPP2R2B gene.
This Month in Archives of Neurology. Arch Neurol. 2010;67(10):1174-1175. doi:10.1001/archneurol.2010.237