Document Detail

Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study.
MedLine Citation:
PMID:  23137949     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Fibrillar amyloid-β (Aβ) is thought to begin accumulating in the brain many years before the onset of clinical impairment in patients with Alzheimer's disease. By assessing the accumulation of Aβ in people at risk of genetic forms of Alzheimer's disease, we can identify how early preclinical changes start in individuals certain to develop dementia later in life. We sought to characterise the age-related accumulation of Aβ deposition in presenilin 1 (PSEN1) E280A mutation carriers across the spectrum of preclinical disease.
METHODS: Between Aug 1 and Dec 6, 2011, members of the familial Alzheimer's disease Colombian kindred aged 18-60 years were recruited from the Alzheimer's Prevention Initiative's registry at the University of Antioquia, Medellín, Colombia. Cross-sectional assessment using florbetapir PET was done in symptomatic mutation carriers with mild cognitive impairment or mild dementia, asymptomatic carriers, and asymptomatic non-carriers. These assessments were done at the Banner Alzheimer's Institute in Phoenix, AZ, USA. A cortical grey matter mask consisting of six predefined regions.was used to measure mean cortical florbetapir PET binding. Cortical-to-pontine standard-uptake value ratios were used to characterise the cross-sectional accumulation of fibrillar Aβ deposition in carriers and non-carriers with regression analysis and to estimate the trajectories of fibrillar Aβ deposition.
FINDINGS: We enrolled a cohort of 11 symptomatic individuals, 19 presymptomatic mutation carriers, and 20 asymptomatic non-carriers, ranging in age from 20 to 56 years. There was greater florbetapir binding in asymptomatic PSEN1 E280A mutation carriers than in age matched non-carriers. Fibrillar Aβ began to accumulate in PSEN 1E280A mutation carriers at a mean age of 28·2 years (95% CI 27·3-33·4), about 16 years and 21 years before the predicted median ages at mild cognitive impairment and dementia onset, respectively. (18)F florbetapir binding rose steeply over the next 9·4 years and plateaued at a mean age of 37·6 years (95% CI 35·3-40·2), about 6 and 11 years before the expected respective median ages at mild cognitive impairment and dementia onset. Prominent florbetapir binding was seen in the anterior and posterior cingulate, precuneus, and parietotemporal and frontal grey matter, as well as in the basal ganglia. Binding in the basal ganglia was not seen earlier or more prominently than in other regions.
INTERPRETATION: 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.
FUNDING: Avid Radiopharmaceuticals, Banner Alzheimer's Foundation, Nomis Foundation, Anonymous Foundation, Forget Me Not Initiative, Colciencias, National Institute on Aging, and the State of Arizona.
Adam S Fleisher; Kewei Chen; Yakeel T Quiroz; Laura J Jakimovich; Madelyn Gutierrez Gomez; Carolyn M Langois; Jessica B S Langbaum; Napatkamon Ayutyanont; Auttawut Roontiva; Pradeep Thiyyagura; Wendy Lee; Hua Mo; Liliana Lopez; Sonia Moreno; Natalia Acosta-Baena; Margarita Giraldo; Gloria Garcia; Rebecca A Reiman; Matthew J Huentelman; Kenneth S Kosik; Pierre N Tariot; Francisco Lopera; Eric M Reiman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-06
Journal Detail:
Title:  The Lancet. Neurology     Volume:  11     ISSN:  1474-4465     ISO Abbreviation:  Lancet Neurol     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-16     Completed Date:  2013-01-18     Revised Date:  2014-08-15    
Medline Journal Info:
Nlm Unique ID:  101139309     Medline TA:  Lancet Neurol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1057-65     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
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MeSH Terms
Alzheimer Disease / diagnosis,  genetics*,  radionuclide imaging*
Amyloid beta-Peptides / metabolism*
Aniline Compounds / diagnostic use,  metabolism*
Cohort Studies
Cross-Sectional Studies
Ethylene Glycols / diagnostic use,  metabolism*
Fluorine Radioisotopes / diagnostic use,  metabolism
Middle Aged
Positron-Emission Tomography* / methods
Presenilin-1 / genetics*
Young Adult
Grant Support
P30 AG019610/AG/NIA NIH HHS; P30 AG19610/AG/NIA NIH HHS; R01 AG031581/AG/NIA NIH HHS; R01 AG031581/AG/NIA NIH HHS
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Aniline Compounds; 0/Ethylene Glycols; 0/Fluorine Radioisotopes; 0/PSEN1 protein, human; 0/Presenilin-1; 6867Q6IKOD/florbetapir
Comment In:
Nat Rev Neurol. 2013 Jan;9(1):4   [PMID:  23165336 ]
Lancet Neurol. 2012 Dec;11(12):1018-20   [PMID:  23137951 ]

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