title: Brain imaging of cognitively normal individuals with 2 parents affected by late-onset AD.
abstract: OBJECTIVE
  This brain imaging study examines whether cognitively normal (NL) individuals with 2 parents affected by late-onset Alzheimer disease (LOAD) show evidence of more extensive Alzheimer disease pathology compared with those who have a single parent affected by LOAD.
  
  
  METHODS
  Fifty-two NL individuals received MRI, (11)C-Pittsburgh compound B (PiB)-PET, and (18)F-fluoro-2-deoxyglucose (FDG)-PET. These included 4 demographically balanced groups (n = 13/group, aged 32-72 years, 60% female, 30% APOE ε4 carriers) of NL individuals with maternal (FHm), paternal (FHp), and maternal and paternal (FHmp) family history of LOAD, and with negative family history (FH-). Statistical parametric mapping, voxel-based morphometry, and z-score mapping were used to compare MRI gray matter volumes (GMVs), partial volume-corrected PiB retention, and FDG metabolism across FH groups and vs FH-.
  
  
  RESULTS
  NL FHmp showed more severe abnormalities in all 3 biomarkers vs the other groups regarding the number of regions affected and magnitude of impairment. PiB retention and hypometabolism were most pronounced in FHmp, intermediate in FHm, and lowest in FHp and FH-. GMV reductions were highest in FHmp and intermediate in FHm and FHp vs FH-. In all FH+ groups, amyloid-β deposition exceeded GMV loss and hypometabolism exceeded GMV loss (p < 0.001), while amyloid-β deposition exceeded hypometabolism in FHmp and FHp but not in FHm.
  
  
  CONCLUSIONS
  These biomarker findings show a "LOAD parent-dose effect" in NL individuals several years, if not decades, before possible clinical symptoms.
authors: From the New York University School of Medicine (L.M., J.M., W.H.T., Y.L., N.S., A.G., S.W., R.O., P.M., L.G., M.J.d.L.); and Weill Cornell Medical College (S.V.), New York.
authors: Lisa
authors: L
authors: Mosconi
authors: John
authors: J
authors: Murray
authors: Wai H
authors: WH
authors: Tsui
authors: Yi
authors: Y
authors: Li
authors: Nicole
authors: N
authors: Spector
authors: Alexander
authors: A
authors: Goldowsky
authors: Schantel
authors: S
authors: Williams
authors: Ricardo
authors: R
authors: Osorio
authors: Pauline
authors: P
authors: McHugh
authors: Lidia
authors: L
authors: Glodzik
authors: Shankar
authors: S
authors: Vallabhajosula
authors: Mony J
authors: MJ
authors: de Leon
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology*; D001284:Atrophy / Q000000981:diagnostic imaging / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D001931:Brain Mapping; D016241:Child of Impaired Parents; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging