title: Greater medial temporal hypometabolism and lower cortical amyloid burden in ApoE4-positive AD patients.
abstract: BACKGROUND
  Apolipoprotein E ε4 (ApoE4) has been associated with an increased risk of Alzheimer's disease (AD), amyloid deposition and hypometabolism. ApoE4 is less prevalent in non-amnestic AD variants suggesting a direct effect on the clinical phenotype. However, the impact of ApoE4 on amyloid burden and glucose metabolism across different clinical AD syndromes is not well understood. We aimed to assess the relationship between amyloid deposition, glucose metabolism and ApoE4 genotype in a clinically heterogeneous population of AD patients.
  
  
  METHODS
  52 patients with probable AD (National Institute on Aging-Alzheimer's Association) underwent [(11)C]Pittsburgh compound B (PIB) and [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. All patients had positive PIB-PET scans. 23 were ApoE4 positive (ApoE4+) (14 heterozygous and 9 homozygous) and 29 were ApoE4 negative (ApoE4-). Groups consisted of language-variant AD, visual-variant AD and AD patients with amnestic and dysexecutive deficits. 52 healthy controls were included for comparison. FDG and PIB uptake was compared between groups on a voxel-wise basis and in regions of interest.
  
  
  RESULTS
  While PIB patterns were diffuse in both patient groups, ApoE4- patients showed higher PIB uptake than ApoE4+ patients across the cortex. Higher PIB uptake in ApoE4- patients was particularly significant in right lateral frontotemporal regions. In contrast, similar patterns of hypometabolism relative to controls were found in both patient groups, mainly involving lateral temporoparietal cortex, precuneus, posterior cingulate cortex and middle frontal gyrus. Comparing patient groups, ApoE4+ subjects showed greater hypometabolism in bilateral medial temporal and right lateral temporal regions, and ApoE4- patients showed greater hypometabolism in cortical areas, including supplementary motor cortex and superior frontal gyrus.
  
  
  CONCLUSIONS
  ApoE4+ AD patients showed lower global amyloid burden and greater medial temporal hypometabolism compared with matched ApoE4- patients. These findings suggest that ApoE4 may increase susceptibility to molecular pathology and modulate the anatomic pattern of neurodegeneration in AD.
authors: Department of Neurology, Memory & Aging Center, University of California, , San Francisco, California, USA.
authors: Manja
authors: M
authors: Lehmann
authors: Pia M
authors: PM
authors: Ghosh
authors: Cindee
authors: C
authors: Madison
authors: Anna
authors: A
authors: Karydas
authors: Giovanni
authors: G
authors: Coppola
authors: James P
authors: JP
authors: O'Neil
authors: Yadong
authors: Y
authors: Huang
authors: Bruce L
authors: BL
authors: Miller
authors: William J
authors: WJ
authors: Jagust
authors: Gil D
authors: GD
authors: Rabinovici
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000378:metabolism* / Q000502:physiology; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18; D005947:Glucose
keywords: ALZHEIMER'S DISEASE; AMYLOID; GENETICS; PET
references: FASEB J. 1996 Nov;10(13):1485-94
references: 8940294
references: Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6820-5
references: 19346482
references: Ann Neurol. 2010 Jan;67(1):122-31
references: 20186853
references: Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10256-61
references: 20479234
references: N Engl J Med. 1996 Mar 21;334(12):752-8
references: 8592548
references: J Comput Assist Tomogr. 1995 Jul-Aug;19(4):541-7
references: 7622680
references: Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9649-53
references: 8415756
references: Neurosci Lett. 1992 Feb 3;135(2):235-8
references: 1625800
references: Neurology. 2004 Jun 8;62(11):1977-83
references: 15184600
references: Nature. 1994 Nov 3;372(6501):92-4
references: 7969426
references: Neuroscience. 2003;122(2):305-15
references: 14614898
references: Neurology. 2009 Apr 28;72(17):1487-94
references: 19339712
references: Neuron. 2009 Aug 13;63(3):287-303
references: 19679070
references: J Neurosci. 1997 Jan 15;17(2):516-29
references: 8987775
references: Acta Neuropathol. 2002 Apr;103(4):363-9
references: 11904756
references: Lancet. 1993 Sep 18;342(8873):697-9
references: 8103819
references: Neurobiol Aging. 2010 Aug;31(8):1275-83
references: 20472326
references: Neurobiol Aging. 1995 May-Jun;16(3):271-8; discussion 278-84
references: 7566337
references: Neuroimage. 2002 Jan;15(1):273-89
references: 11771995
references: Ann Med. 1995 Dec;27(6):663-70
references: 8652146
references: Lancet Neurol. 2013 Feb;12(2):207-16
references: 23332364
references: Cereb Cortex. 2014 May;24(5):1230-46
references: 23283688
references: J Neurochem. 2007 Jun;101(5):1172-84
references: 17286590
references: J Cereb Blood Flow Metab. 1996 Sep;16(5):834-40
references: 8784228
references: Neurology. 2005 Jan 11;64(1):102-7
references: 15642911
references: Neurology. 2009 Nov 10;73(19):1571-8
references: 19901249
references: J Neurosci. 2012 Dec 12;32(50):18227-33
references: 23238736
references: Neurology. 2009 Dec 15;73(24):2061-70
references: 19923550
references: Brain. 2012 Jul;135(Pt 7):2155-68
references: 22637583
references: J Neurol Neurosurg Psychiatry. 1996 Oct;61(4):352-6
references: 8890772
references: Cortex. 2007 Oct;43(7):835-45
references: 17941342
references: Eur J Pharmacol. 2008 Apr 7;583(2-3):312-21
references: 18275953
references: J Alzheimers Dis. 2010;22(1):307-13
references: 20847408
references: Cell. 2012 Mar 16;148(6):1204-22
references: 22424230
references: J Neurosci. 2010 Dec 15;30(50):17035-40
references: 21159973
references: Cogn Behav Neurol. 2003 Dec;16(4):211-8
references: 14665820
references: J Biol Chem. 1995 Aug 25;270(34):19791-9
references: 7649988
references: J Biol Chem. 2012 Feb 17;287(8):5253-66
references: 22158868
references: Neurology. 2013 Jan 22;80(4):359-65
references: 23255822
references: Int Psychogeriatr. 2011 Nov;23(9):1393-404
references: 21729410
references: Neuroimage. 2009 Feb 1;44(3):724-8
references: 19013250
references: Neurodegener Dis. 2008;5(3-4):186-9
references: 18322386
references: Neurology. 2002 Mar 12;58(5):743-50
references: 11889238
references: Sci Transl Med. 2011 Jun 29;3(89):89ra57
references: 21715678
references: Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):284-9
references: 14688411
references: Alzheimers Dement. 2011 May;7(3):263-9
references: 21514250