TUESDAY, Nov. 6 (HealthDay News) -- Young adults carrying a high-penetrance autosomal dominance mutation that causes early-onset Alzheimer's disease (presenilin 1 [PSEN1] E280A) have increased magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and plasma biomarkers of Alzheimer's disease, as well as increased fibrillar amyloid-β (Aβ) deposition at an earlier age than non-carriers, according to two studies published online Nov. 6 in The Lancet Neurology.
Eric M. Reiman, M.D., from the Banner Alzheimer's Institute in Phoenix, and colleagues characterized structural and functional MRI, CSF, and plasma biomarkers in a cohort of 44 young adults, 20 of whom were PSEN1 E280A mutation carriers. The researchers found that carriers had greater right hippocampal and parahippocampal activation, less precuneus and posterior cingulated deactivation, and, in several parietal regions, less grey matter. In addition, mutation carriers had higher CSF and plasma Aβ1-42 concentrations.
Using florbetapir position emission tomography binding, Adam S. Fleisher, M.D., also from the Banner Institute, and colleagues attempted to characterize the age-related accumulation of Aβ deposition in a cohort involving 11 symptomatic PSEN1 E280A mutation carriers, 19 presymptomatic PSEN1 E280A mutation carriers, and 20 asymptomatic non-carriers. The researchers identified elevated florbetapir binding in asymptomatic carriers versus age-matched non-carriers. At a mean age of 28.2 years, fibrillar Aβ began to accumulate, which was about 16 and 21 years before the predicted median ages at mild cognitive impairment and dementia onset, respectively. Over the next 9.4 years, 18F florbetapir binding increased steeply, plateauing at a mean of 37.6 years.
"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," Fleisher and colleagues conclude.
The second study was funded in part by Avid Radiopharmaceuticals, the manufacturer of florbetapir; several authors disclosed financial ties to pharmaceutical companies, including Avid.
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