Link found between Alzheimer's disease and protein regulation in the brain -- hope for new treatments

ScienceDaily (Oct. 22, 2012) — A link has been discovered between Alzheimer's disease and the activity level of a protein called eIF2alpha. This has been reported in a new study conducted at the University of Haifa's Sagol Department of Neurobiology, recently published in the journal Neurobiology of Aging. According to Prof. Kobi Rosenblum, head of the Department, altering the performance of this protein via drug therapy could constitute a treatment for Alzheimer's, which is incurable.

Alzheimer's research in recent years has primarily focused on battling the disease once symptoms have appeared, even though it's known that the disease nests in the brain many years before any symptoms are revealed. In advanced stages of the disease, Prof. Rosenblum explains, small lumps (called plaques) are identified forming in the brain from a protein called amyloid. These plaques, he says, are typical of Alzheimer's sufferers and undermine brain functioning. Much research has been directed at understanding these plaques and trying to eliminate them or restrict their formation and growth.

The new study, conducted by research student Yifat Segev in the Laboratory for Research of Molecular and Cellular Mechanisms Underlying Learning and Memory, which is headed by Prof. Rosenblum, in cooperation with Prof. Danny Michaelson of Tel Aviv University, sought to identify factors that could be linked to Alzheimer's even before the irreversible amyloid plaques are formed, and that are connected to the disease's primary risk factor -- age.

A previous study co-authored by Canadian researchers and Prof. Rosenblum's lab at the University of Haifa, revealed that cognitive abilities could be improved by altering the activity of the eIF2alpha protein, which regulates the creation of proteins in all cells, including nerve cells. That research gave Alzheimer's researchers a glimmer of hope: Perhaps it would be possible to improve cognitive abilities or even prevent cognitive damage in Alzheimer's patients at an early stage of the disease by intervening in the mechanisms that regulate protein generation in nerve cells.

The current study compared mice that expressed the human Apoe4 gene -- a gene known as a central risk factor for Alzheimer's -- with a group of mice with the parallel Apoe3 gene, which does not constitute a risk factor for the disease. Mice in the former group showed a change in the regulating mechanism for protein generation involving the eIF2alpha protein that damaged the cognitive abilities of those mice at a young age. This sort of mechanism change is characteristic of aging, and so also hinted at the tendency of these mice toward premature aging.

According to Segev, this is the first time that a link has been found between the activity of eIF2alpha and the Apoe4 gene in relation to Alzheimer's disease. She noted that modification treatments for the eIF2alpha mechanism are being widely researched and are developing quickly, and so the more we can understand about the connection between this mechanism and Alzheimer's, the more we can find ways to identify and slow the progress of the disease.

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The above story is reprinted from materials provided by University of Haifa.

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Journal Reference:

Yifat Segev, Daniel M. Michaelson, Kobi Rosenblum. ApoE e4 is associated with eIF2a phosphorylation and impaired learning in young mice. Neurobiology of Aging, 2012; DOI: 10.1016/j.neurobiolaging.2012.06.020

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Dose-response relationship between work-related cumulative postural exposure and low back pain: A systematic review

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Daniel Cury Ribeiro1,2,*, Daniela Aldabe3, J. Haxby Abbott4, Gisela Sole1 and Stephan Milosavljevic1

1University of Otago, Centre for Physiotherapy Research, School of Physiotherapy, PO Box 56, Dunedin 9054, New Zealand

2Otago Institute of Sport and Adventure, Otago Polytechnic, Private Bag 1910, Dunedin 9054, New Zealand

3University of Otago, School of Physical Education, Dunedin 9054, New Zealand

4University of Otago, Dunedin School of Medicine, Dunedin 9054, New Zealand ?* Author to whom correspondence should be addressed. Tel: 0064-03-479-3666; fax: 0064-03-479-3676; e-mail: daniel.cury.ribeiro{at}gmail.com Received August 22, 2011. Accepted January 13, 2012. Objectives: To assess the evidence for a dose–response relationship between ROM, duration, and frequency of trunk flexion, and risk of occupational LBP.

Methods: An electronic systematic search was conducted using Medline, Cumulative Index to Nursing and Allied Health Literature, EMBASE, and Scopus databases focusing on cohort and case–control studies. Studies were included if they focused on non-specific LBP and postural exposure, considering ROM, duration, or frequency of trunk flexion as independent variables. No language restriction was imposed. Included studies were assessed for risk of bias using the Newcastle-Ottawa Scale for observational studies and a summary of evidence is presented. Results: Eight studies were included and all were methodologically rated as high quality. The included studies yielded a total of 7023 subjects who were considered for risk analysis. Different outcome measures for postural exposure were adopted making meta-analysis difficult to perform. Conclusions: We could not find a clear dose–response relationship for work posture exposures and LBP. Limited evidence was found for ROM and duration of sustained flexed posture as risk factor for LBP. We found no evidence for frequency of trunk flexion as a risk factor for LBP. © The Author 2012. Published by Oxford University Press on behalf of the British Occupational Hygiene SocietyThis ArticleAnn Occup Hyg (2012) 56 (6): 684-696. doi: 10.1093/annhyg/mes003 First published online: February 22, 2012 Current Issue
Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.

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Children with ADHD find medication frees them to choose between right and wrong, study suggests

ScienceDaily (Oct. 16, 2012) — Children living with ADHD tend to feel they benefit from medication to treat the condition and do not think the medication turns them into 'robots', according to a report published October 17. In fact, they report that medication helps them to control their behaviour and make better decisions. The study, which gives a voice to the children themselves, provides valuable insights into their experiences and the stigma they face.

The ADHD VOICES -- Voices on Identity, Childhood, Ethics and Stimulants -- study has worked with 151 families in the UK and the USA to examine ethical and societal issues surrounding attention deficit hyperactivity disorder (ADHD), particularly the use of treatments such as methylphenidate (Ritalin). The project has been led by biomedical ethicist Dr Ilina Singh from King's College London and was funded by the Wellcome Trust.

Dr Singh and colleagues interviewed children and their families about ADHD, behaviour, medication and identity across four contexts: home, school, the doctor's office and peer groups.

The report is intended not only to highlight ethical and social issues surrounding ADHD but also to help families, doctors, teachers and the children themselves to understand from a child's perspective what it is like to live with ADHD.

"ADHD is a very emotive subject, which inspires passionate debate. Everyone seems to have an opinion about the condition, what causes it, and how to deal with children with ADHD, but the voices of these children are rarely listened to," explains Dr Singh. "Who better to tell us what ADHD is like and how medication affects them than the children themselves?"

Dr Singh points out the controversies that surround providing medication to children with ADHD, which some people argue turns the children into 'robots'. She believes that in many cases and with a correct diagnosis, treatment using stimulants is appropriate and beneficial, particularly if it is complemented by other interventions. The evidence from the children she interviewed suggests that they think medication improves their ability to make their own moral choices.

Glenn (age 10), from the USA, says: "If you're driving in a car, and there's two different ways, and you usually always go this way…and then one day you want to go the other way, but…the ADHD acts as a blocker, so you can't.

"[The medicine] opens the blocker so that you can go [the right] way. But you still have the choice of going the wrong way… It's harder [without medication], that's what's the truth. But it's not like [on medication] you're a robot."

Dr Singh also found that children often did not understand their condition or why they were receiving medication, and many children in the study reported that they had little meaningful contact with their doctors. After the initial evaluation, clinic visits tended to focus on side-effect checks, during which children were weighed and measured. Most children were not asked any questions during these visits.

Roger (age 13), from the UK, says: "I've only just started going to the ADHD clinic, but I haven't actually been to it properly. I've seen the doctor and he's talked about [ADHD] and I get weighed. But...they'll just say parts of what it is but then they'll stop, so they will only say some of it and then change the subject."

Dr Singh argues that children need to be better informed and able to discuss their condition. "Given the ethical concerns that arise from ADHD diagnosis and stimulant drug treatment, it is imperative that children are able to openly discuss the value of diagnosis and different treatments with a trusted professional."

The report concludes with a series of recommendations for how parents, doctors and teachers can help children cope with and better understand the condition, and begin to tackle the stigma that currently exists around it.

Professor Peter Hill, a child and adolescent psychiatrist, says: "We hope that the VOICES Study and the ADHD and Me animations will inspire people to think differently about ADHD, drug treatments and children with behavioural difficulties.

"Behaving differently around these children is the main challenge. We hope that the strategies we have outlined will help improve the interactions with these children and help improve their lives."

Clare Matterson, Director of Medical Humanities and Engagement at the Wellcome Trust, comments: "It is refreshing to hear the voices of children included in the debate about ADHD.

"It is a very emotive subject and despite the fact that these children are at the centre of this debate, they are too often ignored. This report sends a clear message to doctors, teachers and parents about the importance of talking to children about their condition -- and more importantly, listening to what they have to say."

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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Dose-response relationship between work-related cumulative postural exposure and low back pain: A systematic review

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