Risks for Central Nervous System Diseases among Mobile Phone Subscribers: A Danish Retrospective Cohort Study

The aim of this study was to investigate a possible link between cellular telephone use and risks for various diseases of the central nervous system (CNS). We conducted a large nationwide cohort study of 420 095 persons whose first cellular telephone subscription was between 1982 and 1995, who were followed through 2003 for hospital contacts for a diagnosis of a CNS disorder. Standardized hospitalization ratios (SHRs) were derived by dividing the number of hospital contacts in the cohort by the number expected in the Danish population. The SHRs were increased by 10–20% for migraine and vertigo. No associations were seen for amyotrophic lateral sclerosis, multiple sclerosis or epilepsy in women. SHRs decreased by 30–40% were observed for dementia (Alzheimer disease, vascular and other dementia), Parkinson disease and epilepsy among men. In analyses restricted to subscribers of 10 years or more, the SHRs remained similarly increased for migraine and vertigo and similarly decreased for Alzheimer disease and other dementia and epilepsy (in men); the other SHRs were close to unity. In conclusion, the excesses of migraine and vertigo observed in this first study on cellular telephones and CNS disease deserve further attention. An interplay of a healthy cohort effect and reversed causation bias due to prodromal symptoms impedes detection of a possible association with dementia and Parkinson disease. Identification of the factors that result in a healthy cohort might be of interest for elucidation of the etiology of these diseases

Fatal Prion Disease in a Mouse Model of Genetic E200K Creutzfeldt-Jakob Disease

Genetic prion diseases are late onset fatal neurodegenerative disorders linked to pathogenic mutations in the prion protein-encoding gene, PRNP. The most prevalent of these is the substitution of Glutamate for Lysine at codon 200 (E200K), causing genetic Creutzfeldt-Jakob disease (gCJD) in several clusters, including Jews of Libyan origin. Investigating the pathogenesis of genetic CJD, as well as developing prophylactic treatments for young asymptomatic carriers of this and other PrP mutations, may well depend upon the availability of appropriate animal models in which long term treatments can be evaluated for efficacy and toxicity. Here we present the first effective mouse model for E200KCJD, which expresses chimeric mouse/human (TgMHu2M) E199KPrP on both a null and a wt PrP background, as is the case for heterozygous patients and carriers. Mice from both lines suffered from distinct neurological symptoms as early as 5–6 month of age and deteriorated to death several months thereafter. Histopathological examination of the brain and spinal cord revealed early gliosis and age-related intraneuronal deposition of disease-associated PrP similarly to human E200K gCJD. Concomitantly we detected aggregated, proteinase K resistant, truncated and oxidized PrP forms on immunoblots. Inoculation of brain extracts from TgMHu2ME199K mice readily induced, the first time for any mutant prion transgenic model, a distinct fatal prion disease in wt mice. We believe that these mice may serve as an ideal platform for the investigation of the pathogenesis of genetic prion disease and thus for the monitoring of anti-prion treatments

Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data

We are grateful to the families and individuals who took part in the GS:SFHS and UKB studies, and to all those involved in participant recruitment, data collection, sample processing and QC, including academic researchers, clinical staff, laboratory technicians, clerical workers, IT staff, statisticians and research managers. This work is supported by the Wellcome Trust through a Strategic Award, reference 104036/Z/ 14/Z. We acknowledge with gratitude the financial support received from the Dr Mortimer and Theresa Sackler Foundation. This research has been conducted using the GS:SFHS and UK Biobank (project #4844) resources. GS:SFHS received core funding from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. UKB was established using funding from the Wellcome Trust, Medical Research Council, the Scottish Government Department of Health, and the Northwest Regional Development Agency. DJP, IJD, TCR and AMM are members of the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). TCR is supported by Alzheimer's Scotland, through the Marjorie MacBeath bequest. Funding from the Biotechnology and Biological Sciences Research Council and Medical Research Council is gratefully acknowledged. We are grateful for the use of summary data from the International Genomics of Alzheimer's Project and the Major Depressive Disorder working group of the Psychiatric Genomics Consortium.Peer reviewedPublisher PD