title: Familial Alzheimer's disease and inherited prion disease in the UK are poorly ascertained.
abstract: OBJECTIVE
  To ascertain the frequency and geographical distribution of patients diagnosed with known genetic causes of Alzheimer's disease (AD) and inherited prion disease (IPD) in the UK 2001-2005. By comparison with frequencies predicted from published population studies, to estimate the proportion of patients with these conditions who are being accurately diagnosed.
  
  
  METHODS
  All the positive diagnostic test results (from both genetic testing centres) were identified for mutations in presenilin-1 (PSEN1), presenilin-2 (PSEN2), amyloid precursor protein (APP) and prion protein genes (PRNP) for patients resident in the UK in a 5 year period. The variation in the incidence of mutation detection between UK regions was assessed with census population data. Published studies of the genetic epidemiology of familial early onset AD (EOAD) were reviewed to produce estimates of the number of patients in the UK that should be detected.
  
  
  RESULTS
  The rate of detection of EOAD and IPD varied very significantly and consistently between regions of the UK with low rates of detection in Northern and Western Britain (72% less detection in these regions compared with Central and Southeast Britain). The estimates from population studies further suggest a greater number of patients with EOAD than are diagnosed by genetic testing throughout the UK.
  
  
  CONCLUSIONS
  It is likely that patients with EOAD and IPD are not being recognised and referred for testing. With the prospect of meaningful disease modifying therapeutics for these diseases, this study highlights an issue of relevance to neurologists and those planning for provision of National Health Services.
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Stevens
authors.forename: J
authors.initials: J
authors.lastname: Beck
authors.forename: A
authors.initials: A
authors.lastname: Lukic
authors.forename: N
authors.initials: N
authors.lastname: Ryan
authors.forename: S
authors.initials: S
authors.lastname: Abbs
authors.forename: J
authors.initials: J
authors.lastname: Collinge
authors.forename: N C
authors.initials: NC
authors.lastname: Fox
authors.forename: S
authors.initials: S
authors.lastname: Mead
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D005843:Geography; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D053764:Presenilin-1 / Q000235:genetics; D053766:Presenilin-2 / Q000235:genetics; D017096:Prion Diseases / Q000453:epidemiology* / Q000235:genetics; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics; D000077153:Progranulins; D006113:United Kingdom / Q000453:epidemiology; D016875:tau Proteins / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C512656:PRNP protein, human; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D000072002:Prion Proteins; D011328:Prions; D000077153:Progranulins; D016875:tau Proteins