2 Studies Shed Light on Early Development of Alzheimer's

Dorian Martin Health Guide
  • Does the brain start changing many years prior to the onset of Alzheimer’s? Two new studies just published in the Lancet Neurology seem to indicate that the answer is “yes.” And both have implications for better understanding both familial dementia as well as late-onset Alzheimer's.

    One study looked at 44 young adults between the ages of 18 and 26 who were part of the Colombian Alzheimer's Prevention Initiative Registry in Medellín Antioquia, Colombia. Twenty of these study participations had a gene mutation called presenilin 1 (PSEN1) that is responsible for the development of Alzheimer’s at a very early age. Twenty-four of the study participants did not have this mutation. At the time of the study, no participant showed any signs of cognitive decline.

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    The researchers performed scans of the brain as well as other tests on study participants. Their analysis found that there were significant differences in the brain structure and function among those who had the genetic mutation and those who didn’t have it. The participants who had the PSEN1 mutation showed greater activity in the brain’s hippocampus, which is responsible for memory forming, organizing and storing, and the parahippocampus, which has an important role in memory encoding as well as memory retrieval. The researchers also found that these participants had less gray matter in specific portions of the brain as well as cerebrospinal fluid that had increased levels of amyloid beta protein, which is part of the amyloid plaques found in brains with Alzheimer’s disease.

    The researchers noted that people who have the PSEN1 mutation start to show signs of mental decline, on average, around the age of 45. However, biomarkers are evident at least two decades before the symptoms of memory loss first begin to appear.

    "These findings suggest that brain changes begin many years before the clinical onset of Alzheimer's disease, and even before the onset of amyloid plaque deposition,” said Dr. Eric Reiman, executive director of the Banner Alzheimer's Institute in Arizona and the study’s lead author. “They raise new questions about the earliest brain changes involved in the predisposition to Alzheimer's and the extent to which they could be targeted by future prevention therapies.”

    Other researchers believe these findings have important implications. "These findings question our models of Alzheimer's disease on several fronts,” stated Dr. Nick Fox, a professor at University College London’s Institute of Neurology, in a commentary that was included with this study in The Lancet Neurology. “They suggest that neurodegenerative changes occur over 20 years before symptom onset and somewhat earlier than was suggested by previous brain imaging studies of individuals at risk of inherited Alzheimer's disease.”

    The Banner Alzheimer’s Institute research team also conducted a second study under the leadership of Dr. Adam Fleisher that found that amyloid plaques start to accumulate in the brains of people who have the PSEN1 mutation by the time they are in their late 20s. This study involved a cohort of 50 participants who also were part of the Alzheimer’s Prevention Initiative’s registry at the University of Antioquia, Medellin, Columbia. Of this group, 11 were symptomatic, 19 were presymptomatic but had the genetic mutation, and 20 had no symptoms and did not have the genetic mutation.  

  • Using PET imaging technique, the researchers found that amyloid plaque began to build up in participants who had the genetic mutation around the age of 28, which was 16 years prior to the median age of mild cognitive impairment and 21 years before the media age when dementia was diagnosed.

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    “These findings contribute to the understanding of preclinical familial Alzheimer's disease and help set the stage for assessment of amyloid-modifying treatments in the prevention of familial Alzheimer's disease,” the researchers stated.

    Primary Sources for This Sharepost:

    Fleisher, A. S., et al. (2012). Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study. The Lancet Neurology.

    Reiman, E. M., et al. (2012). Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the presenilin 1 E280A kindred: a case-control study. The Lancet Neurology.

Published On: November 12, 2012