Developmental deficits and staging of dynamics of age associated Alzheimer's disease neurodegeneration and neuronal loss in subjects with Down syndrome.
Alzheimer’s disease
Clinicopathological staging
Developmental neuronal deficits
Down syndrome
Lewy bodies
Neurofibrillary degeneration
Neuronal loss
Stereology
TDP-43 neurodegeneration
β-amyloidosis
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
04 01 2022
04 01 2022
Historique:
received:
14
10
2021
accepted:
02
12
2021
entrez:
5
1
2022
pubmed:
6
1
2022
medline:
24
3
2022
Statut:
epublish
Résumé
The increased life expectancy of individuals with Down syndrome (DS) is associated with increased prevalence of trisomy 21-linked early-onset Alzheimer's disease (EOAD) and dementia. The aims of this study of 14 brain regions including the entorhinal cortex, hippocampus, basal ganglia, and cerebellum in 33 adults with DS 26-72 years of age were to identify the magnitude of brain region-specific developmental neuronal deficits contributing to intellectual deficits, to apply this baseline to identification of the topography and magnitude of neurodegeneration and neuronal and volume losses caused by EOAD, and to establish age-based staging of the pattern of genetically driven neuropathology in DS. Both DS subject age and stage of dementia, themselves very strongly correlated, were strong predictors of an AD-associated decrease of the number of neurons, considered a major contributor to dementia. The DS cohort was subclassified by age as pre-AD stage, with 26-41-year-old subjects with a full spectrum of developmental deficit but with very limited incipient AD pathology, and 43-49, 51-59, and 61-72-year-old groups with predominant prevalence of mild, moderately severe, and severe dementia respectively. This multiregional study revealed a 28.1% developmental neuronal deficit in DS subjects 26-41 years of age and 11.9% AD-associated neuronal loss in DS subjects 43-49 years of age; a 28.0% maximum neuronal loss at 51-59 years of age; and a 11.0% minimum neuronal loss at 61-72 years of age. A total developmental neuronal deficit of 40.8 million neurons and AD-associated neuronal loss of 41.6 million neurons reflect a comparable magnitude of developmental neuronal deficit contributing to intellectual deficits, and AD-associated neuronal loss contributing to dementia. This highly predictable pattern of pathology indicates that successful treatment of DS subjects in the fourth decade of life may prevent AD pathology and functional decline.
Identifiants
pubmed: 34983655
doi: 10.1186/s40478-021-01300-9
pii: 10.1186/s40478-021-01300-9
pmc: PMC8728914
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2Subventions
Organisme : NIA NIH HHS
ID : P30 AG066512
Pays : United States
Informations de copyright
© 2021. The Author(s).
Références
J Microsc. 1999 Mar;193(Pt 3):199-211
pubmed: 10348656
Genomics. 2004 Jan;83(1):130-9
pubmed: 14667816
Proc Natl Acad Sci U S A. 1986 Jul;83(13):4913-7
pubmed: 3088567
J Intellect Disabil Res. 1995 Oct;39 ( Pt 5):432-6
pubmed: 8555719
Neurodegeneration. 1996 Jun;5(2):115-20
pubmed: 8819131
Behav Brain Res. 2010 Dec 6;214(1):3-11
pubmed: 20471430
Acta Neuropathol Commun. 2020 Apr 29;8(1):61
pubmed: 32349792
J Neuropathol Exp Neurol. 1990 Sep;49(5):509-20
pubmed: 2148772
Acta Neuropathol. 1998 Feb;95(2):213-6
pubmed: 9498059
J Neurochem. 2008 Mar;104(5):1333-44
pubmed: 18005339
Alzheimers Dement. 2015 Jun;11(6):700-9
pubmed: 25510383
Neurobiol Aging. 2017 May;53:11-19
pubmed: 28192686
Alzheimers Dement. 2020 Jul;16(7):1065-1077
pubmed: 32544310
J Neurodev Disord. 2020 Jan 23;12(1):4
pubmed: 31973697
Br J Psychiatry. 2002 May;180:405-10
pubmed: 11983636
Ann Neurol. 1985 Mar;17(3):278-82
pubmed: 3158266
J Comp Neurol. 1990 Jun 1;296(1):1-22
pubmed: 2358525
Ann Neurol. 1996 Nov;40(5):799-801
pubmed: 8957023
Am J Pathol. 1973 Nov;73(2):457-76
pubmed: 4271339
J Comp Neurol. 1983 Feb 20;214(2):170-97
pubmed: 6841683
Acta Neuropathol. 1991;82(4):239-59
pubmed: 1759558
Neurobiol Aging. 2008 Jun;29(6):828-35
pubmed: 17250929
Acta Neuropathol. 2016 Apr;131(4):571-85
pubmed: 26810071
FASEB J. 2008 Sep;22(9):3224-33
pubmed: 18509201
Acta Neuropathol. 1994;87(3):233-41
pubmed: 8009955
Clin Neuropathol. 1990 Jul-Aug;9(4):181-90
pubmed: 2146054
Am J Pathol. 1998 Nov;153(5):1365-70
pubmed: 9811326
J Neuropathol Exp Neurol. 2011 Jan;70(1):36-50
pubmed: 21157379
Brain. 2019 Jun 1;142(6):1503-1527
pubmed: 31039256
Lancet. 2002 Mar 23;359(9311):1019-25
pubmed: 11937181
J Intellect Disabil Res. 2017 Sep;61(9):843-852
pubmed: 28664561
FEBS J. 2011 Jan;278(2):236-45
pubmed: 21156028
J Neuropathol Exp Neurol. 2008 Jun;67(6):555-64
pubmed: 18520774
Ann Anat. 2008 Nov 20;190(5):421-7
pubmed: 18722098
Hum Mol Genet. 2007 Jan 1;16(1):15-23
pubmed: 17135279
Cereb Cortex. 2020 Jan 10;30(1):382-390
pubmed: 31264685
J Alzheimers Dis. 2021;80(2):683-693
pubmed: 33579840
Brain Res Bull. 1986 Jun;16(6):773-87
pubmed: 2875770
Am J Med Genet Suppl. 1990;7:274-81
pubmed: 2149962
Brain Dev. 2005 Jun;27(4):246-52
pubmed: 15862185
Am J Psychiatry. 2001 Oct;158(10):1659-65
pubmed: 11578999
Arch Neurol. 1995 Apr;52(4):379-91
pubmed: 7710374
Psychopharmacol Bull. 1988;24(4):653-9
pubmed: 3249767
Neuroimage Clin. 2020;25:102139
pubmed: 31887718
Ment Retard Dev Disabil Res Rev. 2007;13(3):237-46
pubmed: 17910085
Hippocampus. 2007;17(8):665-78
pubmed: 17546680
Brain Pathol. 2008 Apr;18(2):180-97
pubmed: 18093248
Acta Neuropathol. 1993;85(6):586-95
pubmed: 8337937
Acta Neuropathol. 2014;127(6):811-24
pubmed: 24659241
J Biol Chem. 1996 Dec 27;271(52):33623-31
pubmed: 8969231
Acta Neuropathol Commun. 2017 Dec 01;5(1):93
pubmed: 29195510
J Neuropathol Exp Neurol. 2017 Jun 1;76(6):439-457
pubmed: 28505333
Can J Neurol Sci. 1993 Feb;20(1):48-51
pubmed: 8467429
FEBS J. 2011 Jan;278(2):223-35
pubmed: 21156027
J Intellect Disabil Res. 2014 Jan;58(1):61-70
pubmed: 23902161
Int Rev Res Ment Retard. 2008 Jan 1;36:103-145
pubmed: 19633729
Int J Clin Pract. 2001 Sep;55(7):442-4
pubmed: 11594252
J Biomed Biotechnol. 2006;2006(3):31825
pubmed: 17047304
Lancet. 1959 Apr 4;1(7075):710
pubmed: 13642857
Neuropathology. 2010 Aug;30(4):408-19
pubmed: 20102526
Ann Neurol. 2007 May;61(5):435-45
pubmed: 17469117
Acta Neuropathol. 2016 May;131(5):659-85
pubmed: 27062261
Neurology. 1985 Jul;35(7):957-61
pubmed: 3159974
Acta Neuropathol. 2021 May;141(5):795-799
pubmed: 33797585
J Neuropathol Exp Neurol. 2018 Jan 1;77(1):2-20
pubmed: 29186501
Neuroimaging Clin N Am. 1995 Feb;5(1):45-57
pubmed: 7743084
Brain. 2021 Aug 17;144(7):2166-2175
pubmed: 33742668
Pediatr Neurol. 2019 Nov;100:67-73
pubmed: 31036426
Neurology. 2001 Apr 10;56(7):972-4
pubmed: 11294940
J Intellect Disabil Res. 2007 Jun;51(Pt. 6):463-77
pubmed: 17493029
Acta Neuropathol. 2019 Mar;137(3):413-436
pubmed: 30734106
J Neuropathol Exp Neurol. 1998 Jul;57(7):674-83
pubmed: 9690671
Exp Neurol. 1998 Apr;150(2):296-304
pubmed: 9527899
Neurobiol Aging. 2010 Oct;31(10):1710-20
pubmed: 18996621
Neuroreport. 1994 Dec 20;5(18):2583-5
pubmed: 7696609
Neurosci Lett. 2007 Feb 8;413(1):77-81
pubmed: 17145134
Acta Neuropathol. 2017 Aug;134(2):171-186
pubmed: 28488154
J Pediatr. 2013 Oct;163(4):1163-8
pubmed: 23885965
Neurobiol Aging. 1990 Jan-Feb;11(1):3-13
pubmed: 2183081
Am J Ment Retard. 1996 Jan;100(4):403-12
pubmed: 8718994
J Neuropathol Exp Neurol. 2021 Jan 1;80(1):21-44
pubmed: 33270870
Neurology. 1980 Jun;30(6):639-44
pubmed: 6446047
Can J Neurol Sci. 1989 Nov;16(4 Suppl):535-42
pubmed: 2553231
Neurology. 1984 Jul;34(7):909-16
pubmed: 6234479
Int J Geriatr Psychiatry. 2008 Nov;23(11):1134-40
pubmed: 18464295
N Engl J Med. 1984 Nov 1;311(18):1187-8
pubmed: 6237262
Dev Neurobiol. 2019 Jul;79(7):716-737
pubmed: 31278851
J Neurol Sci. 1987 Aug;80(1):79-89
pubmed: 2956368
Arch Neurol. 1989 Aug;46(8):849-53
pubmed: 2527024
Acta Neuropathol. 2009 Feb;117(2):125-36
pubmed: 19139911
Acta Neuropathol. 1992;84(2):117-27
pubmed: 1381856
Ann Neurol. 1999 Mar;45(3):353-7
pubmed: 10072050
Lancet Neurol. 2016 May;15(6):622-36
pubmed: 27302127
J Alzheimers Dis. 2007 Mar;11(1):61-76
pubmed: 17361036
Arch Neurol. 2002 Nov;59(11):1764-7
pubmed: 12433264
Acta Neuropathol. 2011 Dec;122(6):703-13
pubmed: 21968532
J Clin Med. 2021 Jul 31;10(15):
pubmed: 34362198
Acta Neuropathol Commun. 2018 Jul 4;6(1):56
pubmed: 29973279
Acta Neuropathol. 2008 Oct;116(4):391-407
pubmed: 18696092
J Alzheimers Dis. 2019;67(1):103-112
pubmed: 30452414
Neurology. 2002 Jun 25;58(12):1791-800
pubmed: 12084879
J Neurol Sci. 1989 Feb;89(2-3):169-79
pubmed: 2522541
Arch Neurol. 2009 Dec;66(12):1483-8
pubmed: 20008652