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   Ground-breaking study characterizes early-stage Alzheimer's abnormalities in   
   the intact brain   
      
      
      
   Posted in: Medical Science News | Medical Research News | Medical Condition   
   News   
      
   Published on May 6, 2015 at 2:39 AM   
      
   Alzheimer's disease (AD) is a neurodegenerative condition that strikes at the   
   heart of what makes us human: the ability to think, to feel, to remember and   
   to communicate with those around us. The tragedy is compounded by the fact   
   that there is currently    
   no cure, no treatment, and no diagnostic method capable of identifying   
   Alzheimer's at its early stages.   
      
   A ground-breaking study has now, for the first time anywhere, characterized   
   early-stage changes that occur inside individual, Alzheimer's-affected cells   
   in the intact brain. Remarkably, the study indicates that even if only a small   
   number of cells is    
   affected, the result is a reduction of electrical activity throughout the   
   cerebral cortex - the area of the brain that serves as the center of higher   
   mental function and cognition.   
      
   The researchers - Drs. Edward Stern and Dana Cohen of Bar-Ilan University and   
   Dr. Tara Spires-Jones of the University of Edinburgh - published their   
   findings in the academic journal on February 19th, 2015.   
      
   A Tangled Web   
      
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   Dr. Edward Stern, the lead author of the study, is a member of Bar-Ilan   
   University's Gonda (Goldschmied) Multidisciplinary Brain Research Center, and   
   also holds an appointment at the MassGeneral Institute for Neurodegenerative   
   Disease at Massachusetts    
   General Hospital in the United States. He explains that the study's dramatic   
   results are due, in part, to the scientists' decision to focus on a   
   seldom-studied brain cell pathology known as "tangles".   
      
   "Alzheimer's disease is associated with three pathologies: cell death,   
   extra-cellular build-up of amyloid plaques, and tangles - the abnormal   
   twisting of the cellular filaments which hold the neuron in its proper shape,"   
   Stern says, adding that tangles    
   are caused by an aberrant form of a protein known as tau.   
      
   "While it was already known that pathological tau is associated with dementia,   
   ours is the first study to reveal the tau-linked changes in cell- and   
   network-based activity that underlies neurodegeneration. Significantly, we   
   found that if even a small    
   number of cells have tangles, this amplifies into a devastating effect across   
   the entire network, characterized by long latencies between spikes of   
   inter-neuron communication, as well as a reduction in the overall level of   
   synaptic activity."   
      
   Recording Network-Based "Conversations" in the Intact Brain   
      
   The researcher's observations were made possible through the use of a   
   technique that allowed them to position electrodes inside individual cells in   
   the intact anaesthetized brains of transgenic mice. Studying these mice -   
   genetically altered to produce    
   the tangle-triggering abnormal tau protein - the scientists measured   
   spontaneous sub-threshold fluctuation of electrical activity. They also   
   observed how neuronal activity patterns change in response to stimulation.   
      
   Experiments performed by Dr. Noa Menkes-Caspi, at the time a doctoral   
   candidate in Stern's lab, demonstrated that pathological tau disrupts the   
   activity of single cells as well as intra-cellular communication in the   
   neocortex. This phenomenon was    
   observed prior to any significant cell death, at a time when only a small   
   fraction of the neurons displayed fully-developed tangles.   
      
   According to Stern, these results indicate that Alzheimer's symptoms - long   
   suspected to be caused by the extra-cellular build-up of amyloid-beta, are   
   also caused by the abnormal accumulation of tau that afflicts individual   
   cells. By reducing the rate at    
   which individual neurons fire, tangles act to suppress synaptic activity in   
   the wider neocortical network, leading to reduced cognitive function. Stern   
   suggests that the two pathologies combine with devastating effect to change   
   the neuronal activity    
   patterns in the brain, causing Alzheimer's disease symptoms.   
      
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   Stern points out that this study represents the first time that an abnormality   
   in neural physiology has been causally linked to changes in brain behavior on   
   the network level. He states that this data may eventually point the way   
   toward an elusive goal    
   of clinical medicine: a method for positively identifying Alzheimer's onset,   
   before it's too late.   
      
   "Now that we have characterized patterns of neocortical electrical activity in   
   the presence of tangle-afflicted cells and amyloid-beta affected brains, it   
   may be possible to screen for these patterns with EEG," he says, referring to   
   electroencephalogram,    
   a non-invasive technique commonly used to identify epilepsy and other brain   
   disorders. "This could someday form the basis of early AD diagnosis."   
      
   Stern also sees these findings as an important step toward the longer-term   
   goal of effective Alzheimer's treatment.   
      
   "The key is to compare pathological to normal neurons, and identify ways in   
   which abnormal neural activity might be reversed," he says. "Since a change in   
   brain cell activity is what causes disease symptoms, a clearer understanding   
   of abnormal neural    
   physiology may bring us closer to what we all want, and what the world needs -   
   a treatment for Alzheimer's disease."   
      
   Source: Bar-Ilan University   
      
      
   http://www.news-medical.net/news/20150506/Ground-breaking-study-   
   haracterizes-early-stage-Alzheimers-abnormalities-in-the-intact-brain.aspx   
      
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