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   Changes linked to Alzheimer's disease evident even in young brains   
      
   A new study finds some of the earliest evidence of brain changes associated   
   with Alzheimer's disease in young people without dementia symptoms who died of   
   unrelated causes. (Kirk McKoy / Los Angeles Times)   
      
   By MELISSA HEALY contact the reporter   
   Scientific Research Human Behavior Biology Alzheimer's Disease Northwestern   
   University   
      
   A new study suggests where and when -- though not yet how -- Alzheimer's may   
   begin   
      
   Study suggests 'Alzheimer's disease is truly a lifelong process,' researcher   
   says   
      
   Scientists know that Alzheimer's disease gains a foothold in a patient's brain   
   years before he or she first stashes car keys in the freezer, or gets lost   
   coming home from the store. But a new study suggests that the changes in the   
   brain that set the    
   stage for Alzheimer's may start decades -- indeed a lifetime -- before   
   dementia symptoms appear.   
      
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   Two proposed Alzheimer's drugs show disappointing results   
   The latest research found that people as young as 20 have detectable levels of   
   beta-amyloid molecules -- the building blocks of the amyloid plaques that are   
   a key physical signs of Alzheimer's -- in a group of brain cells that come   
   under attack in    
   Alzheimer's disease. In older people who were cognitively normal at the time   
   of their death, researchers also found amyloid molecules, usually in greater   
   concentrations and often already clumped together, in those special neurons.   
      
   The scientists looked specifically at the cholinergic neurons in the basal   
   forebrain, which are among the first to sustain damage and to die off in   
   Alzheimer's disease. Researchers found that all of the brains they studied   
   tended to accumulate more    
   amyloid molecules -- and more "clumps" of the sticky protein -- inside those   
   cells with age.    
      
   Their findings appear in the journal Brain.   
      
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   "What this suggests is that Alzheimer's disease is truly a lifelong process,"   
   said the study's lead author, Changiz Geula, a neuroscientist with the   
   Cognitive Neurology and Alzheimer's Disease Center at Northwestern   
   University's Feinberg School of    
   Medicine.   
      
   "If we were to try to prevent the formation of clumps in this population,   
   these findings would suggest we would have to intervene when a person is much,   
   much younger," he added.   
      
   At very low levels of concentration, amyloid molecules appear to be normal and   
   perhaps even perform some valuable function in the basal forebrain's   
   cholinergic neurons, Geula said in an interview. Over time, their   
   concentration appears to build, and they    
   form clumps called oligomers in those cells.   
      
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   Nerve cells in other areas of the brain did not show the same extent of   
   amyloid accumulation. The latest research therefore suggests that these   
   neurons are where Alzheimer's disease starts, and that all people appear to   
   have a supply of its building    
   blocks there. For reasons as yet undiscovered, however, some people collect   
   more amyloid in these neurons than others as they age.   
      
   In many, these concentrations become so dense that the amyloid sticks or   
   clumps together. For an unlucky few, these clumps become so big and so   
   plentiful that they form tough and insoluble clumps -- plaques. Those plaques   
   begin to appear outside the    
   cells, where they cause neurons to die and disrupt electrical signals among   
   the survivors. Problems with memory and executive function become apparent.   
      
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   "The exciting idea implied by this report is that the biology that goes awry   
   in Alzheimer's disease ... may be initially manifest in large neurons in this   
   brain region throughout life," said University of Hawaii neurologist and   
   Alzheimer's disease    
   researcher Dr. Lon White, who was not involved in the latest study.   
      
   If that's so, White added, researchers should plumb the operations of the   
   basal forebrain's cholinergic neurons in early and middle age to discover   
   what, exactly, sets off the trajectory whereby concentrations of amyloid grow   
   unchecked.   
      
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   To discern age-related patterns in the concentration of amyloid in the special   
   cells of the forebrain, scientists drew upon Northwestern University's   
   Alzheimer's Disease Brain Bank and from tissue from other brains contributed   
   by pathologists from other    
   institutions.   
      
   The researchers analyzed brains from 13 cognitively normal people ages 20 to   
   66, 14 people ages 70 to 99 who showed no signs of dementia, 21 individuals   
   ages  60 to 91 who had been diagnosed with Alzheimer's, and "super-aged" two   
   women who, at 90 and 95    
   years old, had performed on memory tests on a par with an average 50- to   
   65-year-old.   
      
   In the cells of the basal forebrain, scientists found that amyloid molecules   
   began accumulating in young adulthood and continued throughout the lifespan.   
   Individuals in their 20s and other normal young individuals showed amyloid and   
   some signs of early    
   clumping. But the clumps in older individuals and those with Alzheimer's were   
   larger.   
      
   White praised researchers for studying the brains of people who died   
   prematurely of other causes in a bid to capture the earliest seeds of   
   Alzheimer's disease.   
      
   "In order to understand what goes wrong in the pathogenesis of clinical   
   Alzheimer's disease, we must understand the biochemical and physiologic   
   aspects of amyloid biology not just in old, demented persons who have come to   
   autopsy, but in the normal brain    
   at all ages," he said.   
      
   Follow me on Twitter @LATMelissaHealy and "like" Los Angeles Times Science &   
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   http://www.latimes.com/science/sciencenow/la-sci-sn-alzheimers-c   
   anges-young-brains-20150302-story.html   
      
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