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Posted by on Nov 13, 2012 in Genetics, Neurology

Pathology of Alzheimer Disease Found 20-30 Years Before Onset of Clinical Dementia

Pathology of Alzheimer Disease Found 20-30 Years Before Onset of Clinical Dementia

Bolstering the idea that Alzheimer disease begins decades before clinical dementia is apparent, new data suggest that functional and structural brain changes as well as increased levels of amyloid beta (a hallmark of AD) are already present in at-risk young adults. In a cohort study from the Colombian Alzheimer’s Prevention Initiative Registry, 18-26-year-old carriers of presenilin 1 (PSEN1), a deterministic gene for AD, were more likely to show greater activation (or less deactivation) of memory-critical parts of the brain, less gray matter in other parts of the brain (ie, “several parietal regions”), and elevated levels of amyloid beta 1-42 in the CSF and plasma than noncarriers.* The authors of the study, the results of which were published in the latest issue of Lancet Neurology, could not say whether the underlying brain changes were neurodegenerative or developmental.**

In a companion study, also published in Lancet Neurology, evidence of significantly increased amyloid deposition in the brain (as measured by florbetapir binding on PET images) was seen at a mean age of 28 years in PSEN1 carriers (vs noncarriers). By assessing older carriers (up to 56 years of age), the study authors found that amyloid deposition “rose steeply” during the next 9-10 years and plateaued thereafterabout 10-15 years before the typical onset of dementia in these cases of familial AD.

CSF = cerebrospinal fluid; PET = positron emission tomography.

* People who carry the PSEN1 gene in this extended Colombian
family typically show clinical AD (eg, dementia) in their 40s and 50s.

** An underlying caveat of the study is that it was relatively small. There
were 20 gene carriers and 24 noncarriers, and only 10 people in each
cohort underwent lumbar puncture for CSF analysis.

bmartin (1127 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.