title: Low platelet iPLA₂ activity predicts conversion from mild cognitive impairment to Alzheimer's disease: a 4-year follow-up study.
abstract: Reduced phospholipase A₂ (PLA₂) activity has been reported in the brain and in blood cells of patients with Alzheimer's disease (AD). Individuals with mild cognitive impairment (MCI) are at increased risk of developing AD. In the present study, we determined the activity of distinct PLA₂ subgroups (iPLA₂, sPLA₂ and cPLA₂) in older adults with MCI as compared to patients with mild dementia due to AD and to cognitively healthy controls. We investigated whether decreased PLA₂ activity at baseline is associated with the progression of MCI to AD upon follow-up during a period of 4 years. The activity of PLA₂ subgroups was determined in platelets from 169 elderly adults. Progression of MCI to AD was ascertained by standard clinical criteria for AD upon follow-up. At baseline, iPLA₂ activity was significantly decreased (p = 0.001) in patients with AD and MCI as compared to controls. Patients with MCI who progressed to AD during follow-up showed significantly lower iPLA₂ activity at baseline as compared to patients with MCI who did not progress to AD (p = 0.009). Moreover, subjects from the control group at baseline who progressed to MCI during follow-up had lower sPLA₂ and cPLA₂ (p = 0.014 and p = 0.009, respectively). Our findings suggest that low platelet iPLA₂ activity may be a risk marker for AD in subjects with MCI. Moreover, low sPLA₂ and cPLA₂ were related to cognitive decline in healthy controls, suggesting a relationship with the very early stages of the disease.
authors.affiliation: Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil, gattaz@usp.br.
authors.forename: Wagner F
authors.initials: WF
authors.lastname: Gattaz
authors.forename: Leda L
authors.initials: LL
authors.lastname: Talib
authors.forename: Evelin L
authors.initials: EL
authors.lastname: Schaeffer
authors.forename: Breno S
authors.initials: BS
authors.lastname: Diniz
authors.forename: Orestes V
authors.initials: OV
authors.lastname: Forlenza
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis*; D060825:Cognitive Dysfunction / Q000097:blood* / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D054522:Group VI Phospholipases A2 / Q000097:blood*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human
references.citation: J Psychiatr Res. 1975 Nov;12(3):189-98
references.pmid: 1202204
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2012 Apr;86(4-5):149-53
references.pmid: 22498046
references.citation: J Neural Transm (Vienna). 2007;114(8):1033-9
references.pmid: 17447002
references.citation: Psychopharmacology (Berl). 2005 Sep;181(2):392-400
references.pmid: 15830227
references.citation: J Neural Transm (Vienna). 2007 Feb;114(2):231-8
references.pmid: 17131232
references.citation: Eur Arch Psychiatry Clin Neurosci. 1996;246(3):129-31
references.pmid: 8739397
references.citation: J Lipid Res. 2009 Apr;50 Suppl:S237-42
references.pmid: 19011112
references.citation: Glia. 1999 Aug;27(2):110-28
references.pmid: 10417811
references.citation: Braz J Psychiatry. 2008 Dec;30(4):316-21
references.pmid: 19142405
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2010 Jan;82(1):57-60
references.pmid: 19726172
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2008 Apr-May;78(4-5):265-9
references.pmid: 18467085
references.citation: Exp Brain Res. 2002 Mar;143(2):191-7
references.pmid: 11880895
references.citation: Psychopharmacology (Berl). 2008 May;198(1):1-27
references.pmid: 18392810
references.citation: Braz J Psychiatry. 2010 Sep;32(3):216-22
references.pmid: 20414590
references.citation: Clin Chem. 2009 Dec;55(12):2171-9
references.pmid: 19850632
references.citation: Biol Psychiatry. 1995 Jan 1;37(1):13-7
references.pmid: 7893853
references.citation: J Neural Transm (Vienna). 2009 Jan;116(1):41-50
references.pmid: 18982240
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2010 Dec 1;34(8):1381-9
references.pmid: 20804810
references.citation: J Lipid Res. 2013 Oct;54(10):2884-97
references.pmid: 23868911
references.citation: Brain Res. 1996 May 20;721(1-2):39-48
references.pmid: 8793082
references.citation: Biochim Biophys Acta. 2006 Nov;1761(11):1246-59
references.pmid: 16973413
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2013 Sep;89(4):265-8
references.pmid: 23880350
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2011 Aug 15;35(7):1612-7
references.pmid: 21601609
references.citation: J Neurochem. 1997 Aug;69(2):704-12
references.pmid: 9231730
references.citation: J Biol Chem. 1994 May 6;269(18):13057-60
references.pmid: 8175726
references.citation: Arch Neurol. 1999 Mar;56(3):303-8
references.pmid: 10190820
references.citation: Psychopharmacology (Berl). 2009 Jan;202(1-3):37-51
references.pmid: 18853146
references.citation: Ann N Y Acad Sci. 1996 Jan 17;777:310-5
references.pmid: 8624105
references.citation: Curr Top Med Chem. 2012;12(21):2314-23
references.pmid: 23279172
references.citation: J Biol Chem. 2005 Jun 17;280(24):23203-14
references.pmid: 15781456
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2004 Sep;71(3):161-9
references.pmid: 15253885
references.citation: Neurochem Int. 2000 Jul;37(1):17-31
references.pmid: 10781842
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2007 Jan;76(1):47-55
references.pmid: 17187973
references.citation: J Neural Transm (Vienna). 2007 Mar;114(3):379-85
references.pmid: 17066253
references.citation: Platelets. 2006 Nov;17(7):484-92
references.pmid: 17074725
references.citation: J Neural Transm (Vienna). 2011 Sep;118(9):1273-9
references.pmid: 21387172
references.citation: J Lipid Res. 2004 Feb;45(2):205-13
references.pmid: 14657205
references.citation: Neurosci Lett. 2006 Apr 24;397(3):214-8
references.pmid: 16406345
references.citation: Dement Geriatr Cogn Disord. 2009;28(6):507-12
references.pmid: 19996595
references.citation: Neurology. 1984 Jul;34(7):939-44
references.pmid: 6610841
references.citation: Int J Geriatr Psychiatry. 2008 Nov;23(11):1127-33
references.pmid: 18464287
references.citation: J Biol Chem. 2005 Jul 29;280(30):28044-52
references.pmid: 15927955
references.citation: Neurobiol Aging. 2010 Nov;31(11):1877-84
references.pmid: 19070941
references.citation: J Neurosci Res. 2002 Nov 1;70(3):462-73
references.pmid: 12391607
references.citation: Annu Rev Biochem. 2008;77:495-520
references.pmid: 18405237
references.citation: J Neuropathol Exp Neurol. 1988 May;47(3):235-48
references.pmid: 3367156
references.citation: Biochem J. 2008 Jan 15;409(2):429-38
references.pmid: 17868035
references.citation: Biochem Biophys Res Commun. 1993 Nov 30;197(1):292-7
references.pmid: 8250938
references.citation: Psychopharmacology (Berl). 2005 Jul;180(2):359-65
references.pmid: 15700180
references.citation: FEBS Lett. 2005 May 9;579(12):2693-701
references.pmid: 15862311
references.citation: J Neural Transm (Vienna). 2004 May;111(5):591-601
references.pmid: 15088152
references.citation: Neuromolecular Med. 2010 Jun;12(2):133-48
references.pmid: 19855947
references.citation: J Neuroinflammation. 2006 Oct 07;3:28
references.pmid: 17026770
references.citation: J Alzheimers Dis. 2010;22(4):1305-11
references.pmid: 20930310
references.citation: Alzheimer Dis Assoc Disord. 2006 Apr-Jun;20(2 Suppl 1):S12-8
references.pmid: 16772751
references.citation: Br J Psychiatry. 1986 Dec;149:698-709
references.pmid: 3790869
references.citation: J Neural Transm (Vienna). 2002 May;109(5-6):623-31
references.pmid: 12111454
references.citation: Neurobiol Dis. 1996 Feb;3(1):51-63
references.pmid: 9173912
references.citation: J Neural Transm (Vienna). 2010 Aug;117(8):919-47
references.pmid: 20632195