title: Parkinson's disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies.
abstract: Dementia is increasingly being recognized in cases of Parkinson's disease (PD); such cases are termed PD dementia (PDD). The spread of fibrillar α-synuclein (α-syn) pathology from the brainstem to limbic and neocortical structures seems to be the strongest neuropathological correlate of emerging dementia in PD. In addition, up to 50% of patients with PDD also develop sufficient numbers of amyloid-β plaques and tau-containing neurofibrillary tangles for a secondary diagnosis of Alzheimer's disease, and these pathologies may act synergistically with α-syn pathology to confer a worse prognosis. An understanding of the relationships between these three distinct pathologies and their resultant clinical phenotypes is crucial for the development of effective disease-modifying treatments for PD and PDD.
authors.affiliation: Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Alzheimer's Disease Core Center, Institute on Aging, University of Pennsylvania Perelman School of Medicine, HUP, Maloney 3rd Floor, 36th and Spruce Streets, Philadelphia, Pennsylvania 19104-4283, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Irwin
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000502:physiology*; D001921:Brain / Q000473:pathology / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000473:pathology / Q000502:physiology; D010300:Parkinson Disease / Q000473:pathology* / Q000503:physiopathology; D051844:alpha-Synuclein / Q000502:physiology*; D016875:tau Proteins / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins
references.citation: Nat Rev Neurosci. 2013 Jan;14(1):38-48
references.pmid: 23254192
references.citation: Science. 1997 Jun 27;276(5321):2045-7
references.pmid: 9197268
references.citation: Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12245-50
references.pmid: 11572944
references.citation: Lancet Neurol. 2012 Aug;11(8):697-707
references.pmid: 22814541
references.citation: Exp Neurol. 2008 Oct;213(2):315-25
references.pmid: 18625222
references.citation: Neurology. 2005 Apr 26;64(8):1404-10
references.pmid: 15851731
references.citation: J Neural Transm Suppl. 2006;(70):89-97
references.pmid: 17017514
references.citation: J Neurosci. 2011 Jul 6;31(27):10076-87
references.pmid: 21734300
references.citation: Brain Pathol. 2000 Jul;10(3):378-84
references.pmid: 10885656
references.citation: Ann Neurol. 2002 Jun;51(6):722-9
references.pmid: 12112078
references.citation: Neurology. 2005 Oct 25;65(8):1239-45
references.pmid: 16247051
references.citation: J Parkinsons Dis. 2011;1(3):277-86
references.pmid: 23939308
references.citation: Neurology. 2005 Jun 28;64(12):2069-73
references.pmid: 15985574
references.citation: JAMA Neurol. 2013 Feb;70(2):223-8
references.pmid: 23407718
references.citation: Neurology. 1999 Dec 10;53(9):1974-82
references.pmid: 10599768
references.citation: Acta Neuropathol. 2008 Apr;115(4):427-36
references.pmid: 18273624
references.citation: Science. 2003 Oct 31;302(5646):841
references.pmid: 14593171
references.citation: J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):852-6
references.pmid: 12810766
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13010-5
references.pmid: 19651612
references.citation: Ann Neurol. 2005 Jan;57(1):82-91
references.pmid: 15562510
references.citation: J Neural Transm Suppl. 2007;(72):91-104
references.pmid: 17982882
references.citation: Mov Disord. 1998 Nov;13(6):885-94
references.pmid: 9827611
references.citation: Neurodegener Dis. 2007;4(6):428-30
references.pmid: 17934326
references.citation: Mov Disord. 2008 Dec 15;23(16):2303-6
references.pmid: 19006193
references.citation: Neurology. 2007 Mar 13;68(11):812-9
references.pmid: 17353469
references.citation: Mov Disord. 2013 Jan;28(1):31-40
references.pmid: 23390095
references.citation: Hum Mol Genet. 1999 Apr;8(4):711-5
references.pmid: 10072441
references.citation: Science. 2012 Nov 16;338(6109):949-53
references.pmid: 23161999
references.citation: Arch Neurol. 1993 Feb;50(2):140-8
references.pmid: 8431132
references.citation: Brain. 2010 Jun;133(Pt 6):1755-62
references.pmid: 20371510
references.citation: Arch Neurol. 2012 Nov;69(11):1445-52
references.pmid: 22925882
references.citation: Ann Neurol. 1994 May;35(5):513-29
references.pmid: 8179297
references.citation: J Neural Transm (Vienna). 2011 May;118(5):713-9
references.pmid: 21479514
references.citation: Cochrane Database Syst Rev. 2012 Mar 14;(3):CD006504
references.pmid: 22419314
references.citation: Neurology. 2010 Nov 16;75(20):1766-72
references.pmid: 20962290
references.citation: JAMA Neurol. 2013 Jun;70(6):727-35
references.pmid: 23588557
references.citation: Neurology. 2012 Sep 11;79(11):1161-7
references.pmid: 22933741
references.citation: N Engl J Med. 2009 Oct 22;361(17):1651-61
references.pmid: 19846850
references.citation: Acta Neuropathol. 2008 Apr;115(4):437-44
references.pmid: 18264713
references.citation: Mov Disord. 2002 Nov;17(6):1161-5
references.pmid: 12465052
references.citation: Acta Neuropathol. 2008 Apr;115(4):417-25
references.pmid: 18185940
references.citation: J Neurol. 2010 Mar;257(3):359-66
references.pmid: 19795154
references.citation: Arch Neurol. 2002 Jan;59(1):102-12
references.pmid: 11790237
references.citation: J Neural Transm (Vienna). 2002 Mar;109(3):329-39
references.pmid: 11956955
references.citation: J Neural Transm (Vienna). 2004 Oct;111(10-11):1219-35
references.pmid: 15480835
references.citation: Am J Pathol. 1998 Nov;153(5):1365-70
references.pmid: 9811326
references.citation: Parkinsonism Relat Disord. 2007;13 Suppl 3:S221-4
references.pmid: 18267239
references.citation: J Exp Med. 2012 May 7;209(5):975-86
references.pmid: 22508839
references.citation: J Neurol Neurosurg Psychiatry. 1985 May;48(5):413-21
references.pmid: 3998751
references.citation: J Neurol. 2013 Feb;260(2):438-44
references.pmid: 22911513
references.citation: Mov Disord. 2013 Mar;28(3):302-10
references.pmid: 23408705
references.citation: Mov Disord. 2010 Jul 15;25(9):1170-6
references.pmid: 20310053
references.citation: Neurology. 2012 Dec 11;79(24):2307-14
references.pmid: 23152586
references.citation: Brain. 2010 Mar;133(Pt 3):713-26
references.pmid: 20157014
references.citation: Neurology. 2000 May 23;54(10):1916-21
references.pmid: 10822429
references.citation: JAMA Neurol. 2013 Oct;70(10):1277-87
references.pmid: 23979011
references.citation: Acta Neuropathol. 2001 Oct;102(4):355-63
references.pmid: 11603811
references.citation: Acta Neuropathol. 2011 Aug;122(2):187-204
references.pmid: 21720849
references.citation: Acta Neuropathol. 2002 Jul;104(1):7-11
references.pmid: 12070658
references.citation: Mov Disord. 2010;25 Suppl 1:S78-82
references.pmid: 20187227
references.citation: Nature. 1997 Aug 28;388(6645):839-40
references.pmid: 9278044
references.citation: J Neurol Neurosurg Psychiatry. 2010 Oct;81(10):1080-6
references.pmid: 20547614
references.citation: Arch Neurol. 1998 Jul;55(7):969-78
references.pmid: 9678315
references.citation: Neurobiol Aging. 2003 Mar-Apr;24(2):197-211
references.pmid: 12498954
references.citation: J Neural Transm (Vienna). 2010 Oct;117(10):1177-81
references.pmid: 20730548
references.citation: Neurology. 1990 Oct;40(10):1529-34
references.pmid: 2215943
references.citation: Mol Neurobiol. 2013 Apr;47(2):495-508
references.pmid: 22622968
references.citation: Trends Neurosci. 2004 Mar;27(3):129-34
references.pmid: 15036877
references.citation: Mov Disord. 2006 Aug;21(8):1123-30
references.pmid: 16637023
references.citation: Ann Neurol. 2011 Mar;69(3):570-80
references.pmid: 21400565
references.citation: Prog Brain Res. 2010;184:53-87
references.pmid: 20887870
references.citation: J Neuropathol Exp Neurol. 2005 Feb;64(2):156-62
references.pmid: 15751230
references.citation: Brain. 2009 Jul;132(Pt 7):1783-94
references.pmid: 19286695
references.citation: Mov Disord. 2010 Nov 15;25(15):2682-5
references.pmid: 20818673
references.citation: Neurology. 2013 Jan 8;80(2):176-80
references.pmid: 23296128
references.citation: Brain. 2009 Nov;132(Pt 11):2947-57
references.pmid: 19759203
references.citation: Mov Disord. 2002 Nov;17(6):1221-6
references.pmid: 12465060
references.citation: Int J Biochem Cell Biol. 2008;40(9):1835-49
references.pmid: 18291704
references.citation: J Neuropathol Exp Neurol. 2003 Jun;62(6):644-54
references.pmid: 12834109
references.citation: Neurobiol Aging. 2012 Sep;33(9):2225-8
references.pmid: 21813214
references.citation: Neurology. 2006 Nov 14;67(9):1605-11
references.pmid: 17101891
references.citation: Neuron. 2002 May 16;34(4):521-33
references.pmid: 12062037
references.citation: Neurology. 2010 Sep 21;75(12):1055-61
references.pmid: 20720189
references.citation: Neurology. 2013 Jan 1;80(1):85-91
references.pmid: 23243071
references.citation: Neuropathology. 2004 Mar;24(1):72-8
references.pmid: 15068176
references.citation: Mov Disord. 2013 Mar;28(3):296-301
references.pmid: 23239424
references.citation: Nat Med. 2008 May;14(5):501-3
references.pmid: 18391963
references.citation: Sci Transl Med. 2012 Feb 15;4(121):121ra20
references.pmid: 22344688
references.citation: Ann Neurol. 2007 Aug;62(2):145-53
references.pmid: 17683088
references.citation: J Alzheimers Dis. 2006;9(3 Suppl):417-23
references.pmid: 16914880
references.citation: Acta Neuropathol. 2003 Jul;106(1):83-8
references.pmid: 12687392
references.citation: Alzheimer Dis Assoc Disord. 2009 Jul-Sep;23(3):295-7
references.pmid: 19812474
references.citation: J Neurosci. 2010 May 26;30(21):7281-9
references.pmid: 20505094
references.citation: J Neurol Neurosurg Psychiatry. 2013 May;84(5):537-43
references.pmid: 23117496
references.citation: Ann Neurol. 1983 Mar;13(3):243-8
references.pmid: 6847136
references.citation: JAMA Neurol. 2013 Apr;70(4):462-8
references.pmid: 23380910
references.citation: Brain Lang. 2012 Jan;120(1):52-60
references.pmid: 21962945
references.citation: Mov Disord. 2009 Nov 15;24(15):2203-10
references.pmid: 19795497
references.citation: Mov Disord. 2011 Oct;26 Suppl 3:S42-80
references.pmid: 22021174
references.citation: Brain. 2011 May;134(Pt 5):1493-1505
references.pmid: 21596773
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20051-6
references.pmid: 19892735
references.citation: Neurology. 2000 Aug 22;55(4):539-44
references.pmid: 10953188
references.citation: Mov Disord. 2010 Jun 15;25(8):969-78
references.pmid: 20535823
references.citation: Acta Neuropathol. 2007 Sep;114(3):221-9
references.pmid: 17653732
references.citation: J Neurol. 2009 Mar;256(3):493-8
references.pmid: 19308307
references.citation: Parkinsonism Relat Disord. 2011 Jan;17(1):61-4
references.pmid: 21044858
references.citation: Neurology. 2003 May 27;60(10):1586-90
references.pmid: 12771246
references.citation: Acta Neuropathol. 2008 Apr;115(4):399-407
references.pmid: 18297293
references.citation: Arch Neurol. 2009 Nov;66(11):1353-8
references.pmid: 19901166
references.citation: Adv Neurol. 1990;53:245-9
references.pmid: 2239463
references.citation: Science. 2003 Apr 25;300(5619):636-40
references.pmid: 12714745
references.citation: Arch Neurol. 2003 Mar;60(3):387-92
references.pmid: 12633150
references.citation: N Engl J Med. 1985 Sep 19;313(12):728-31
references.pmid: 3929089
references.citation: Neurology. 2012 Nov 6;79(19):1944-50
references.pmid: 23035075
references.citation: Acta Neuropathol. 1998 May;95(5):450-4
references.pmid: 9600590
references.citation: Nat Rev Neurol. 2013 Jan;9(1):13-24
references.pmid: 23183883
references.citation: J Neurol. 2007 Jan;254(1):38-45
references.pmid: 17508138
references.citation: Ann Neurol. 2008 Dec;64 Suppl 2:S93-100
references.pmid: 19127573
references.citation: J Neuropathol Exp Neurol. 2002 May;61(5):413-26
references.pmid: 12030260
references.citation: Exp Neurol. 2009 Dec;220(2):224-5
references.pmid: 19786018
references.citation: Alzheimer Dis Assoc Disord. 2009 Jul-Sep;23(3):229-33
references.pmid: 19812464
references.citation: Nat Med. 2008 May;14(5):504-6
references.pmid: 18391962
references.citation: Neuron. 2006 Oct 5;52(1):33-8
references.pmid: 17015225
references.citation: Mov Disord. 2007 Sep 15;22(12):1689-707; quiz 1837
references.pmid: 17542011
references.citation: Arch Neurol. 2009 May;66(5):578-83
references.pmid: 19433657
references.citation: Ann Neurol. 2007 Aug;62(2):137-44
references.pmid: 17514749
references.citation: Nat Med. 1998 Nov;4(11):1318-20
references.pmid: 9809558
references.citation: Acta Neuropathol. 2008 Apr;115(4):409-15
references.pmid: 18231798
references.citation: Ann Neurol. 2012 Oct;72(4):587-98
references.pmid: 23037886
references.citation: Mov Disord. 2012 Apr;27(4):512-8
references.pmid: 22344634
references.citation: Acta Neuropathol. 2009 Jun;117(6):613-34
references.pmid: 19399512
references.citation: Prog Neurobiol. 2011 Dec;95(4):629-35
references.pmid: 21930184
references.citation: Neurobiol Aging. 2005 Aug-Sep;26(8):1183-92
references.pmid: 15917102
references.citation: Mov Disord. 2008 Apr 30;23(6):837-44
references.pmid: 18307261
references.citation: Acta Neuropathol. 2012 Jan;123(1):1-11
references.pmid: 22101365
references.citation: Science. 1982 Apr 9;216(4542):136-44
references.pmid: 6801762
references.citation: Brain. 2013 Apr;136(Pt 4):1128-38
references.pmid: 23466394
references.citation: Parkinsonism Relat Disord. 2012 Sep;18(8):941-7
references.pmid: 22595621
references.citation: Pharmacol Ther. 2013 Jun;138(3):311-22
references.pmid: 23384597
references.citation: Acta Neuropathol. 2008 Jul;116(1):1-16
references.pmid: 18592254
references.citation: Brain Pathol. 2008 Apr;18(2):220-4
references.pmid: 18241240
references.citation: J Neuropathol Exp Neurol. 2008 Feb;67(2):155-61
references.pmid: 18219254
references.citation: Brain. 2012 Jan;135(Pt 1):170-80
references.pmid: 22108576
references.citation: Cell Death Differ. 2011 Sep;18(9):1425-33
references.pmid: 21566660
references.citation: Acta Neuropathol. 2006 Sep;112(3):253-60
references.pmid: 16804711
references.citation: Acta Neuropathol. 2000 Sep;100(3):285-90
references.pmid: 10965798
references.citation: Ann Neurol. 2011 Apr;69(4):655-63
references.pmid: 21520231
references.citation: Mov Disord. 2012 Mar;27(3):349-56
references.pmid: 22275317
references.citation: Brain. 2009 Nov;132(Pt 11):2958-69
references.pmid: 19812213
references.citation: Neuron. 2011 Oct 6;72(1):57-71
references.pmid: 21982369
references.citation: Neurosci Lett. 2011 Jan 7;487(2):169-73
references.pmid: 20951764
references.citation: Alzheimers Dement. 2011 May;7(3):280-92
references.pmid: 21514248
references.citation: J Nucl Med. 2011 Jun;52(6):848-55
references.pmid: 21571793
references.citation: Arch Neurol. 2012 Oct;69(10):1326-31
references.pmid: 22825369
references.citation: Neurology. 2006 Dec 12;67(11):1931-4
references.pmid: 17159096
references.citation: Mov Disord. 2012 Jun;27(7):831-42
references.pmid: 22451330
references.citation: Ann Neurol. 2002 Aug;52(2):205-10
references.pmid: 12210791