Neuropathology of incidental Lewy body & prodromal Parkinson's disease.
Enteric nervous system (ENS)
Incidental Lewy body disease (iLBD)
Lewy body α-Synuclein
Prodromal Parkinson’s disease (PD)
REM-sleep behaviour disorder (RBD)
Journal
Molecular neurodegeneration
ISSN: 1750-1326
Titre abrégé: Mol Neurodegener
Pays: England
ID NLM: 101266600
Informations de publication
Date de publication:
12 05 2023
12 05 2023
Historique:
received:
01
02
2023
accepted:
21
04
2023
medline:
15
5
2023
pubmed:
13
5
2023
entrez:
12
5
2023
Statut:
epublish
Résumé
Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with a loss of dopaminergic (DA) neurons. Despite symptomatic therapies, there is currently no disease-modifying treatment to halt neuronal loss in PD. A major hurdle for developing and testing such curative therapies results from the fact that most DA neurons are already lost at the time of the clinical diagnosis, rendering them inaccessible to therapy. Understanding the early pathological changes that precede Lewy body pathology (LBP) and cell loss in PD will likely support the identification of novel diagnostic and therapeutic strategies and help to differentiate LBP-dependent and -independent alterations. Several previous studies identified such specific molecular and cellular changes that occur prior to the appearance of Lewy bodies (LBs) in DA neurons, but a concise map of such early disease events is currently missing. Here, we conducted a literature review to identify and discuss the results of previous studies that investigated cases with incidental Lewy body disease (iLBD), a presumed pathological precursor of PD. Collectively, our review demonstrates numerous cellular and molecular neuropathological changes occurring prior to the appearance of LBs in DA neurons. Our review provides the reader with a summary of early pathological events in PD that may support the identification of novel therapeutic and diagnostic targets and aid to the development of disease-modifying strategies in PD.
Sections du résumé
BACKGROUND
Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with a loss of dopaminergic (DA) neurons. Despite symptomatic therapies, there is currently no disease-modifying treatment to halt neuronal loss in PD. A major hurdle for developing and testing such curative therapies results from the fact that most DA neurons are already lost at the time of the clinical diagnosis, rendering them inaccessible to therapy. Understanding the early pathological changes that precede Lewy body pathology (LBP) and cell loss in PD will likely support the identification of novel diagnostic and therapeutic strategies and help to differentiate LBP-dependent and -independent alterations. Several previous studies identified such specific molecular and cellular changes that occur prior to the appearance of Lewy bodies (LBs) in DA neurons, but a concise map of such early disease events is currently missing.
METHODS
Here, we conducted a literature review to identify and discuss the results of previous studies that investigated cases with incidental Lewy body disease (iLBD), a presumed pathological precursor of PD.
RESULTS
Collectively, our review demonstrates numerous cellular and molecular neuropathological changes occurring prior to the appearance of LBs in DA neurons.
CONCLUSIONS
Our review provides the reader with a summary of early pathological events in PD that may support the identification of novel therapeutic and diagnostic targets and aid to the development of disease-modifying strategies in PD.
Identifiants
pubmed: 37173733
doi: 10.1186/s13024-023-00622-7
pii: 10.1186/s13024-023-00622-7
pmc: PMC10182593
doi:
Substances chimiques
alpha-Synuclein
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
32Informations de copyright
© 2023. The Author(s).
Références
J Neural Transm (Vienna). 2019 Aug;126(8):933-995
pubmed: 31214855
Science. 1997 Jun 27;276(5321):2045-7
pubmed: 9197268
J Mol Neurosci. 2015 Sep;57(1):48-62
pubmed: 25982926
Brain. 2012 Jun;135(Pt 6):1860-70
pubmed: 22561644
Brain. 2021 May 7;144(4):1118-1126
pubmed: 33855335
Prog Neurobiol. 2021 Apr;199:101919
pubmed: 33039415
Neurology. 2007 Jul 24;69(4):356-9
pubmed: 17646627
Sleep Med Rev. 2019 Feb;43:37-46
pubmed: 30503716
Sci Rep. 2020 Oct 23;10(1):17631
pubmed: 33097764
Mov Disord. 2017 May;32(5):722-723
pubmed: 28513078
Sleep Med Rev. 2017 Aug;34:23-33
pubmed: 27542516
J Neurosci Res. 2009 Mar;87(4):1002-13
pubmed: 18855937
Mol Neurodegener. 2012 Aug 24;7:42
pubmed: 22920859
Eur J Neurol. 2007 Jul;14(7):721-8
pubmed: 17594326
Brain. 2020 Oct 1;143(10):3077-3088
pubmed: 32830221
Biomolecules. 2015 Jul 16;5(3):1467-79
pubmed: 26193328
Sleep. 2013 Dec 01;36(12):1885-92
pubmed: 24293763
Brain. 2004 Jun;127(Pt 6):1332-42
pubmed: 15090472
CNS Neurol Disord Drug Targets. 2015;14(7):947-55
pubmed: 25801839
EMBO Mol Med. 2013 Jul;5(7):1119-27
pubmed: 23703938
Am J Pathol. 1996 Jan;148(1):267-72
pubmed: 8546215
J Neurol. 2014 Jun;261(6):1112-8
pubmed: 24687894
Neurology. 2006 Dec 26;67(12):2236-8
pubmed: 17190953
Mov Disord. 2018 Oct;33(10):1580-1590
pubmed: 30294923
Mov Disord. 2007 Aug 15;22(11):1581-6
pubmed: 17523195
Sleep Med. 2010 Apr;11(4):361-5
pubmed: 20223708
J Neurochem. 2009 Nov;111(3):696-702
pubmed: 19694908
Mov Disord. 2002 May;17(3):501-8
pubmed: 12112197
Neuropathol Appl Neurobiol. 2006 Jun;32(3):284-95
pubmed: 16640647
J Neural Transm (Vienna). 2019 May;126(5):585-595
pubmed: 30911822
J Exp Med. 2016 Aug 22;213(9):1759-78
pubmed: 27503075
Parkinsonism Relat Disord. 2007 May;13(4):214-8
pubmed: 17275395
Mov Disord. 2014 Apr;29(4):454-62
pubmed: 24619848
Cell Tissue Res. 2004 Oct;318(1):121-34
pubmed: 15338272
N Engl J Med. 2022 Aug 4;387(5):466-467
pubmed: 35921458
Science. 2012 Nov 16;338(6109):949-53
pubmed: 23161999
Neurobiol Dis. 2020 Jul;141:104876
pubmed: 32339655
J Parkinsons Dis. 2017;7(s1):S71-S85
pubmed: 28282810
J Neural Transm (Vienna). 2019 Apr;126(4):423-431
pubmed: 29943229
J Neural Transm (Vienna). 2011 May;118(5):713-9
pubmed: 21479514
Sleep Med Rev. 2018 Oct;41:266-274
pubmed: 29784534
Int J Mol Sci. 2023 Mar 21;24(6):
pubmed: 36982988
Mov Disord. 2017 Nov;32(11):1504-1523
pubmed: 29124790
Ann Neurol. 2014 Mar;75(3):351-62
pubmed: 24243558
Mov Disord. 2010 Apr 15;25(5):642-6
pubmed: 20175211
Am J Hum Genet. 2014 Dec 4;95(6):729-35
pubmed: 25434005
Mov Disord. 2014 Jan;29(1):41-53
pubmed: 24167038
Neurology. 2014 Nov 4;83(19):1739-46
pubmed: 25298306
Brain. 2013 Aug;136(Pt 8):2419-31
pubmed: 23884810
Ann Neurol. 2018 Mar;83(3):562-574
pubmed: 29420861
J Neurosci. 2007 Feb 7;27(6):1405-10
pubmed: 17287515
N Engl J Med. 2009 Oct 22;361(17):1651-61
pubmed: 19846850
Acta Neuropathol. 2008 Apr;115(4):437-44
pubmed: 18264713
Sci Rep. 2016 Feb 16;6:20863
pubmed: 26878893
Lancet Neurol. 2021 Mar;20(3):203-212
pubmed: 33609478
J Neurol Neurosurg Psychiatry. 1988 Jun;51(6):745-52
pubmed: 2841426
Neurology. 1999 Apr 12;52(6):1269-71
pubmed: 10214756
J Neural Transm (Vienna). 2004 Oct;111(10-11):1219-35
pubmed: 15480835
Nat Genet. 1998 Feb;18(2):106-8
pubmed: 9462735
Lancet. 2004 Sep 25-Oct 1;364(9440):1167-9
pubmed: 15451224
PLoS One. 2015 Jun 18;10(6):e0128651
pubmed: 26087293
J Neuropathol Exp Neurol. 2004 Jul;63(7):742-9
pubmed: 15290899
Neuropathol Appl Neurobiol. 2008 Jun;34(3):284-95
pubmed: 18053026
Acta Neuropathol Commun. 2021 Apr 7;9(1):62
pubmed: 33827706
Brain. 1999 Aug;122 ( Pt 8):1437-48
pubmed: 10430830
Neuron. 2015 Aug 19;87(4):699-715
pubmed: 26291156
J Proteome Res. 2021 Aug 6;20(8):3913-3924
pubmed: 34191522
Acta Neuropathol. 2017 Mar;133(3):381-393
pubmed: 28012041
Pharmacol Ther. 2007 Jan;113(1):210-26
pubmed: 17125841
Neurodegener Dis. 2007;4(6):424-7
pubmed: 17934325
Neurogenetics. 2006 Mar;7(1):1-11
pubmed: 16344956
Brain Res. 2005 Mar 10;1037(1-2):1-6
pubmed: 15777746
JAMA Neurol. 2013 May;70(5):571-9
pubmed: 23459986
Neurology. 1999 Oct 12;53(6):1284-91
pubmed: 10522886
Neurology. 2012 Dec 11;79(24):2307-14
pubmed: 23152586
Neurol Sci. 2013 Jun;34(6):935-40
pubmed: 22843227
Mov Disord. 2014 Mar;29(3):410-5
pubmed: 24488760
Brain. 2016 Aug;139(Pt 8):2224-34
pubmed: 27297241
Nature. 1997 Aug 28;388(6645):839-40
pubmed: 9278044
Brain. 2016 Apr;139(Pt 4):1180-8
pubmed: 26920675
Neurology. 2021 May 18;96(20):e2513-e2524
pubmed: 33837116
Neurology. 1997 Aug;49(2):610-3
pubmed: 9270609
J Parkinsons Dis. 2021;11(4):1833-1843
pubmed: 34151862
Front Neurol. 2020 Sep 30;11:569446
pubmed: 33101177
Neurobiol Aging. 2003 Mar-Apr;24(2):197-211
pubmed: 12498954
Neuroimage Clin. 2020;26:102185
pubmed: 32050136
Neurobiol Aging. 2008 Mar;29(3):408-17
pubmed: 17166629
Brain Res. 1988 Jul 5;455(1):148-52
pubmed: 3416180
Arch Neurol. 2008 Aug;65(8):1074-80
pubmed: 18695057
J Neuroinflammation. 2018 May 1;15(1):129
pubmed: 29716614
Brain. 2009 Dec;132(Pt 12):3298-307
pubmed: 19843648
Lancet Neurol. 2018 Jul;17(7):618-628
pubmed: 29866443
Acta Neuropathol. 1996;91(5):475-81
pubmed: 8740227
J Neurosci. 2009 Oct 28;29(43):13543-56
pubmed: 19864567
BMJ Open. 2019 Oct 7;9(10):e029740
pubmed: 31594876
Lancet Neurol. 2004 Aug;3(8):496-503
pubmed: 15261611
Acta Neuropathol Commun. 2022 Sep 6;10(1):133
pubmed: 36068646
Mov Disord. 2016 Nov;31(11):1711-1719
pubmed: 27250871
Acta Neuropathol. 2009 Dec;118(6):777-84
pubmed: 19802627
Behav Brain Res. 2009 Dec 1;204(1):1-31
pubmed: 19523490
Acta Neuropathol. 2008 Apr;115(4):445-51
pubmed: 17985144
Mol Cancer. 2018 Feb 19;17(1):44
pubmed: 29455644
Antioxid Redox Signal. 2015 Aug 20;23(6):550-64
pubmed: 26094487
Mov Disord. 2015 Oct;30(12):1600-11
pubmed: 26474317
Cereb Cortex. 2018 Feb 1;28(2):658-671
pubmed: 28591814
Lancet Neurol. 2015 Jan;14(1):57-64
pubmed: 25435387
Biochem Pharmacol. 2014 Apr 15;88(4):508-16
pubmed: 24462903
Brain. 2007 Jun;130(Pt 6):1586-95
pubmed: 17491094
Mov Disord. 2018 Jan;33(1):48-57
pubmed: 28843014
Brain. 1991 Oct;114 ( Pt 5):2283-301
pubmed: 1933245
Acta Neuropathol Commun. 2014 Aug 07;2:90
pubmed: 25099483
Brain. 2019 Oct 1;142(10):3116-3128
pubmed: 31504212
Am J Med. 2022 Aug;135(8):1001-1007
pubmed: 35580718
Neurology. 2005 May 24;64(10):1716-20
pubmed: 15911797
Nat Med. 2008 May;14(5):501-3
pubmed: 18391963
Mov Disord. 2005 Feb;20(2):164-71
pubmed: 15468109
Neurology. 2005 Feb 8;64(3):545-7
pubmed: 15699393
Biochim Biophys Acta. 2009 Jul;1792(7):730-40
pubmed: 18718530
Mov Disord. 2002 Nov;17(6):1166-73
pubmed: 12465053
Neurology. 2012 Dec 11;79(24):2298-9
pubmed: 23152588
Neurology. 1999 Dec 10;53(9):2003-9
pubmed: 10599772
Neurosci Lett. 2009 Apr 3;453(2):77-80
pubmed: 19356597
Trends Neurosci. 2015 Mar;38(3):178-88
pubmed: 25639775
Neurobiol Dis. 2014 Aug;68:190-9
pubmed: 24830390
Nature. 2015 Jun 18;522(7556):340-4
pubmed: 26061766
Parkinsonism Relat Disord. 2014 Nov;20(11):1260-2
pubmed: 25172126
Am J Alzheimers Dis Other Demen. 2008 Feb-Mar;23(1):97-102
pubmed: 18276962
Ann Neurol. 1989 Oct;26(4):551-7
pubmed: 2817829
J Neuropathol Exp Neurol. 2003 Dec;62(12):1241-53
pubmed: 14692700
Mov Disord. 2004 Oct;19(10):1196-202
pubmed: 15390014
Am J Pathol. 2011 Nov;179(5):2152-6
pubmed: 21907175
Nat Neurosci. 2019 Jul;22(7):1099-1109
pubmed: 31235907
Front Aging Neurosci. 2022 Oct 12;14:957705
pubmed: 36313019
Brain. 2000 Jun;123 ( Pt 6):1155-60
pubmed: 10825354
Front Pharmacol. 2022 Mar 03;13:837890
pubmed: 35308220
Nat Rev Neurol. 2012 May 15;8(6):329-39
pubmed: 22584158
Am J Pathol. 1996 Aug;149(2):728-9
pubmed: 8702011
Front Neurol. 2021 Jun 14;12:677213
pubmed: 34194385
Neuroscience. 1990;38(1):245-53
pubmed: 1979431
Mov Disord. 2020 Jul;35(7):1233-1238
pubmed: 32338403
N Engl J Med. 2022 Aug 4;387(5):408-420
pubmed: 35921450
Brain. 2019 Jul 1;142(7):2051-2067
pubmed: 31111143
Ann Neurol. 2015 May;77(5):895-901
pubmed: 25675938
Acta Neuropathol. 2008 Apr;115(4):399-407
pubmed: 18297293
Lancet Neurol. 2010 Nov;9(11):1070-7
pubmed: 20846908
Mov Disord. 2014 Sep;29(10):1244-51
pubmed: 24996051
Electrophoresis. 2018 Dec;39(24):3096-3103
pubmed: 30168606
J Neural Transm (Vienna). 2011 May;118(5):821-39
pubmed: 20862500
Neurology. 2018 Oct 30;91(18):e1710-e1715
pubmed: 30258025
Sleep. 2010 Jun;33(6):767-73
pubmed: 20550017
Ann Clin Transl Neurol. 2016 Aug 28;3(10):812-818
pubmed: 27752516
Hum Mol Genet. 2015 Mar 1;24(5):1336-49
pubmed: 25343991
JAMA Neurol. 2015 Jan;72(1):100-5
pubmed: 25401511
Ann Neurol. 1990 Apr;27(4):373-85
pubmed: 1972319
Mov Disord. 1993 Jul;8(3):315-20
pubmed: 8341295
Nat Rev Neurol. 2013 Jan;9(1):13-24
pubmed: 23183883
N Engl J Med. 2022 Aug 4;387(5):421-432
pubmed: 35921451
Ann Clin Transl Neurol. 2015 Apr;2(4):433-8
pubmed: 25909088
Brain. 2020 May 1;143(5):1462-1475
pubmed: 32380543
Brain. 2017 Dec 1;140(12):3191-3203
pubmed: 29140481
Acta Neuropathol. 2020 Feb;139(2):319-345
pubmed: 31768670
Acta Neuropathol. 2010 Jun;119(6):703-13
pubmed: 20229352
BMJ Open. 2020 Nov 23;10(11):e040527
pubmed: 33234645
J Neurol Sci. 1997 Oct 3;151(1):83-7
pubmed: 9335015
Nat Med. 2008 May;14(5):504-6
pubmed: 18391962
Mov Disord. 2013 Nov;28(13):1847-53
pubmed: 24130124
Science. 2004 May 21;304(5674):1158-60
pubmed: 15087508
Nat Genet. 2014 Sep;46(9):989-93
pubmed: 25064009
Brain Pathol. 2018 May;28(3):315-333
pubmed: 28321951
J Neural Transm (Vienna). 2012 Jan;119(1):59-71
pubmed: 21748523
Acta Neuropathol. 2020 Jul;140(1):49-62
pubmed: 32342188
Ann Neurol. 2012 Jun;71(6):850-4
pubmed: 22718549
Exp Neurol. 1999 Mar;156(1):138-48
pubmed: 10192785
Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S203-6
pubmed: 22166435
Trends Neurosci. 2019 Feb;42(2):140-149
pubmed: 30509690
Neuropathology. 2007 Oct;27(5):494-506
pubmed: 18018486
Arch Neurol. 2006 Apr;63(4):584-8
pubmed: 16606773
Brain Res. 1997 Nov 14;775(1-2):24-9
pubmed: 9439824
Brain. 2019 Sep 1;142(9):2828-2844
pubmed: 31324919
Brain. 2020 Dec 1;143(12):3717-3733
pubmed: 33118032
Brain Res. 2012 Oct 2;1476:183-202
pubmed: 22560500
Neurology. 1996 Dec;47(6 Suppl 3):S161-70
pubmed: 8959985
Acta Neuropathol. 2008 Apr;115(4):409-15
pubmed: 18231798
Neurobiol Dis. 2020 Dec;146:105086
pubmed: 32971232
Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S28-30
pubmed: 22166446
Acta Neuropathol. 2009 Jun;117(6):613-34
pubmed: 19399512
Acta Neuropathol Commun. 2017 Feb 2;5(1):12
pubmed: 28148299
EMBO J. 2018 Sep 14;37(18):
pubmed: 30065071
Adv Anat Embryol Cell Biol. 2009;201:1-119
pubmed: 19230552
Ann Neurol. 2008 Feb;63(2):167-73
pubmed: 18067173
PLoS Genet. 2007 Jun;3(6):e98
pubmed: 17571925
Acta Neuropathol. 2010 Aug;120(2):131-43
pubmed: 20563819
Nat Rev Neurol. 2021 Jun;17(6):349-361
pubmed: 33879872
J Psychiatr Res. 2020 Dec;131:102-107
pubmed: 32950706
J Cereb Blood Flow Metab. 2020 Mar;40(3):552-562
pubmed: 30741074
Front Neurosci. 2016 Jan 14;9:507
pubmed: 26834537
Ann Neurol. 1992;32 Suppl:S82-7
pubmed: 1510385
Brain. 1996 Jun;119 ( Pt 3):823-30
pubmed: 8673494
Histol Histopathol. 1991 Jul;6(3):373-80
pubmed: 1725760
Neuropathology. 2012 Feb;32(1):13-22
pubmed: 22243359
Nat Rev Neurosci. 2021 Apr;22(4):209-222
pubmed: 33608673
Acta Neuropathol. 2008 Jul;116(1):1-16
pubmed: 18592254
Brain. 2013 Apr;136(Pt 4):1128-38
pubmed: 23466394
Ann Neurol. 2010 Jun;67(6):715-25
pubmed: 20517933
Acta Neuropathol. 2021 Sep;142(3):449-474
pubmed: 34309761
Neurology. 2015 Nov 10;85(19):1670-9
pubmed: 26468408
Nat Rev Dis Primers. 2018 Aug 30;4(1):19
pubmed: 30166532
Mov Disord. 2018 Jan;33(1):88-98
pubmed: 28843021
Ann Neurol. 2008 Nov;64(5):485-91
pubmed: 19067353
Nat Genet. 2020 May;52(5):482-493
pubmed: 32341526
Ann Clin Transl Neurol. 2020 Jan;7(1):26-35
pubmed: 31820587
Ann Neurol. 2016 Jun;79(6):1026-30
pubmed: 27016314
Acta Neuropathol. 2000 Sep;100(3):285-90
pubmed: 10965798
Brain Res. 2014 Apr 22;1559:26-32
pubmed: 24602694
Mov Disord. 2012 Apr 15;27(5):656-65
pubmed: 22508284
J Neural Transm (Vienna). 1997;104(6-7):661-77
pubmed: 9444566
Cell Death Dis. 2021 Sep 17;12(10):854
pubmed: 34535638
J Neurol. 2020 Dec;267(12):3673-3682
pubmed: 32676768
Parkinsonism Relat Disord. 2017 May;38:41-47
pubmed: 28242255
J Neurol Sci. 2011 Nov 15;310(1-2):100-6
pubmed: 21689832
Mov Disord. 2009 Oct 15;24(13):1906-9
pubmed: 19645057
Mov Disord. 2012 Jun;27(7):831-42
pubmed: 22451330
Brain. 2019 Mar 1;142(3):744-759
pubmed: 30789229
Exp Neurol. 2013 Aug;246:72-83
pubmed: 22285449
Lancet Neurol. 2017 Oct;16(10):789-796
pubmed: 28684245