title: Pupil response biomarkers distinguish amyloid precursor protein mutation carriers from non-carriers.
abstract: BACKGROUND
  Alzheimer's disease (AD) is usually only diagnosed many years after pathology begins. Earlier detection would allow emerging interventions to have a greater chance to preserve healthy brain function. A rare form of Alzheimer's disease, caused by autosomal-dominant mutations, affects carriers with 100% certainty and at a younger age specific to their mutation. Studying families with these mutations allows a unique investigation of the temporal sequence of biomarker changes in Alzheimer's disease.
  
  
  OBJECTIVE
  To determine whether the pupil flash response (PFR), previously reported to be altered in sporadic Alzheimer's disease, is different in pre-symptomatic mutation carriers.
  
  
  METHODS
  Researchers blinded to participant mutation status collected pupil response data from cognitively normal participants in the Dominantly Inherited Alzheimer's Network (DIAN) Study during 2010-2011.
  
  
  METHODS
  The pupil response was examined at the McCusker Alzheimer's Research Foundation in Perth, Western Australia.
  
  
  METHODS
  Participants were from a single family harboring an Amyloid-Beta Precursor Protein genetic mutation (APPGlu693Gln). Six carriers and six non-carriers were available for pupil testing (age 43.0±8.3 years old, 2 males and 10 females, 4 with hypertension).
  
  
  METHODS
  Pupil response parameter comparison between mutation carriers and non-carriers.
  
  
  RESULTS
  75% recovery time was longer in mutation carriers (p<0.0003, ROC AUC 1.000, Sensitivity 100%, Specificity 100%) and percentage recovery 3.5 seconds after stimulus was less in mutation carriers (p<0.006, ROC AUC 1.000, Sensitivity 100%, Specificity 100%).
  
  
  CONCLUSIONS
  PFR changes occur pre-symptomatically in autosomal dominant AD mutation carriers, supporting further investigation of PFR for early detection of AD.
authors.affiliation: McCusker Alzheimer's Research Foundation, Suite 22, Hollywood Medical Centre, 85 Monash Ave, Nedlands, WA 6009, Australia. ralph.martins@ecu.edu.au.
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Frost
authors.forename: Yogesan
authors.initials: Y
authors.lastname: Kanagasingam
authors.forename: Hamid R
authors.initials: HR
authors.lastname: Sohrabi
authors.forename: Kevin
authors.initials: K
authors.lastname: Taddei
authors.forename: Randall
authors.initials: R
authors.lastname: Bateman
authors.forename: John
authors.initials: J
authors.lastname: Morris
authors.forename: Tammie
authors.initials: T
authors.lastname: Benzinger
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D015415:Biomarkers; D042241:Early Diagnosis; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011680:Pupil / Q000502:physiology*
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers
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