title: Decreased platelet APP isoform ratios in autosomal dominant Alzheimer's disease: baseline data from a DIAN cohort subset.
abstract: BACKGROUND
  This study examines platelet amyloid precursor protein (APP) isoform ratios of 120KDa to 110KDa (APPr) between mutation carriers (MC) carrying a mutation for autosomal dominant Alzheimer's disease (ADAD) and non-carriers (NC). Two previous studies reported no significant difference in APPr between ADAD MC and NC, which may have been due to the small sample size in both studies. The current study examines APPr in MC versus NC in a larger sample. In addition, it investigated whether APPr correlate with neuroimaging data, neuropsychological data and cerebrospinal fluid biomarkers in a cohort subset derived from the Dominantly Inherited Alzheimer Network (DIAN) study.
  
  
  METHODS
  APPr were quantified by western blotting. Fifteen MC (symptomatic and asymptomatic) were compared against twelve NC using univariate general linear model. All participants underwent neuroimaging and neuropsychological testing which were correlated with APPr using Pearson's correlation coefficient (r).
  
  
  RESULTS
  APPr were lower in MC compared to NC (p=0.003) while Mini-Mental State Examination (MMSE) scores were not significantly different (p>0.1). Furthermore, APPr inversely correlated with amyloid imaging in the Caudate Nucleus (r=-0.505; p<0.05) and Precuneus (r=-0.510; p<0.05).
  
  
  CONCLUSIONS
  APPr are lower in ADAD MC compared to NC, and inversely correlated with brain amyloid load prior to significant differences in cognitive health. However, the use of APPr as a biomarker needs to be explored further.
authors: Pratishtha
authors: P
authors: Chatterjee
authors: Veer B
authors: VB
authors: Gupta
authors: Anne M
authors: AM
authors: Fagan
authors: Mateusz S
authors: MS
authors: Jasielec
authors: Chengjie
authors: C
authors: Xiong
authors: Hamid R
authors: HR
authors: Sohrabi
authors: Satvinder
authors: S
authors: Dhaliwal
authors: Kevin
authors: K
authors: Taddei
authors: Pierrick
authors: P
authors: Bourgeat
authors: Belinda M
authors: BM
authors: Brown
authors: Tammie
authors: T
authors: Benzinger
authors: Randall J
authors: RJ
authors: Bateman
authors: John C
authors: JC
authors: Morris
authors: School of Medical Science, Edith Cowan University, 270 Joondalup Dr., Joondalup, WA 6027, Australia. r.martins@ecu.edu.au.
authors: Ralph N
authors: RN
authors: Martins
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000235:genetics / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000097:blood*; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics*; D015153:Blotting, Western; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D006801:Humans; D007536:Isomerism; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography; D013844:Thiazoles; D014904:Western Australia / Q000453:epidemiology
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D013844:Thiazoles
references: Exp Gerontol. 2010 Jan;45(1):53-6
references: 19699790
references: J Neurosci. 2007 Jun 6;27(23):6174-84
references: 17553989
references: Arch Neurol. 1998 Sep;55(9):1195-200
references: 9740113
references: Alzheimer Dis Assoc Disord. 2004 Jan-Mar;18(1):32-4
references: 15195460
references: Brain. 2008 Jul;131(Pt 7):1845-53
references: 18583368
references: Dis Markers. 2008;24(3):151-6
references: 18334736
references: Arch Neurol. 1996 Nov;53(11):1162-6
references: 8912490
references: J Neurol Sci. 2001 Jan 15;183(1):85-8
references: 11166800
references: J Clin Neurosci. 2013 May;20(5):644-8
references: 23453155
references: Am J Med Genet. 1993 Oct 15;48(3):129-30
references: 8291565
references: Prog Neuropsychopharmacol Biol Psychiatry. 2004 Aug;28(5):763-70
references: 15363602
references: Curr Proteomics. 2011 Oct;8(3):216-228
references: 22308104
references: J Biol Chem. 1998 Mar 13;273(11):6277-84
references: 9497354
references: J Biol Chem. 1990 Sep 15;265(26):15977-83
references: 2118534
references: Cell. 1989 Apr 7;57(1):115-26
references: 2649245
references: J Neural Transm (Vienna). 2012 Jul;119(7):815-9
references: 22573143
references: J Alzheimers Dis. 2007 Mar;11(1):77-84
references: 17361037
references: Dis Markers. 2006;22(3):119-25
references: 16788245
references: Int Psychogeriatr. 2009 Aug;21(4):672-87
references: 19470201
references: Neurology. 2001 Dec 26;57(12):2243-8
references: 11756604
references: Neurology. 1997 Jun;48(6):1508-10
references: 9191756
references: Neurology. 2004 Feb 10;62(3):498-501
references: 14872043
references: Immun Ageing. 2012 Sep 17;9(1):20
references: 22985434
references: Mitochondrion. 2006 Dec;6(6):323-30
references: 17123871
references: Neuroimaging Clin N Am. 2005 Nov;15(4):869-77, xi-xii
references: 16443497
references: J Neurol Sci. 2006 Jan 15;240(1-2):53-8
references: 16256140
references: Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):E4502-9
references: 24194552
references: Alzheimer Dis Assoc Disord. 1995 Winter;9(4):213-7
references: 8749610
references: Biochem Biophys Res Commun. 1995 Aug 4;213(1):96-103
references: 7639768
references: J Alzheimers Dis. 2011;25(1):103-9
references: 21368381
references: Am J Psychiatry. 1987 Jul;144(7):860-8
references: 3605398
references: Arch Neurol. 1997 Feb;54(2):139-44
references: 9041854
references: J Neural Transm (Vienna). 2004 May;111(5):591-601
references: 15088152
references: Mol Med. 2002 Feb;8(2):67-74
references: 12080182
references: Mol Med. 2000 Oct;6(10):816-24
references: 11126197
references: Nat Med. 1996 Aug;2(8):864-70
references: 8705854
references: Neurochem Res. 2013 Jul;38(7):1415-23
references: 23575575
references: N Engl J Med. 2012 Aug 30;367(9):795-804
references: 22784036
references: Int J Immunopathol Pharmacol. 2011 Apr-Jun;24(2):529-34
references: 21658330
references: Arch Neurol. 1998 Sep;55(9):1179-80
references: 9740110
references: Neurology. 2000 May 23;54(10):1907-9
references: 10822427