title: Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Avid Radiopharmaceuticals, Banner Alzheimer's Foundation, Nomis Foundation, Anonymous Foundation, Forget Me Not Initiative, Colciencias, National Institute on Aging, and the State of Arizona.
authors.affiliation: Banner Alzheimer's Institute, Phoenix, AZ, USA. adam.fleisher@bannerhealth.com
authors.forename: Adam S
authors.initials: AS
authors.lastname: Fleisher
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.forename: Yakeel T
authors.initials: YT
authors.lastname: Quiroz
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Jakimovich
authors.forename: Madelyn Gutierrez
authors.initials: MG
authors.lastname: Gomez
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Langois
authors.forename: Jessica B S
authors.initials: JB
authors.lastname: Langbaum
authors.forename: Napatkamon
authors.initials: N
authors.lastname: Ayutyanont
authors.forename: Auttawut
authors.initials: A
authors.lastname: Roontiva
authors.forename: Pradeep
authors.initials: P
authors.lastname: Thiyyagura
authors.forename: Wendy
authors.initials: W
authors.lastname: Lee
authors.forename: Hua
authors.initials: H
authors.lastname: Mo
authors.forename: Liliana
authors.initials: L
authors.lastname: Lopez
authors.forename: Sonia
authors.initials: S
authors.lastname: Moreno
authors.forename: Natalia
authors.initials: N
authors.lastname: Acosta-Baena
authors.forename: Margarita
authors.initials: M
authors.lastname: Giraldo
authors.forename: Gloria
authors.initials: G
authors.lastname: Garcia
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Reiman
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Huentelman
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kosik
authors.forename: Pierre N
authors.initials: PN
authors.lastname: Tariot
authors.forename: Francisco
authors.initials: F
authors.lastname: Lopera
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000378:metabolism*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005026:Ethylene Glycols / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D053764:Presenilin-1 / Q000235:genetics*; D012042:Registries; D055815:Young Adult
chemical_list: D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D005026:Ethylene Glycols; D005462:Fluorine Radioisotopes; C508853:PSEN1 protein, human; D053764:Presenilin-1; C545186:florbetapir