Review

Down syndrome: A curative prospect?

  • Received: 15 March 2020 Accepted: 29 May 2020 Published: 22 June 2020
  • Experimental work regarding corrective actions on chromosomes and genes, and control of gene products is yielding promising results. It opens the way to advances in dealing with the etiological aspects of Down syndrome and may lead to important changes in the life of individuals affected with this condition. A small number of molecules are being investigated in pharmacological research that may have positive effects on intellectual functioning. Studies of the pathological consequences of the amyloid cascade and the TAU pathology in the etiology of Alzheimer disease (AD), which is more frequent and occuring earlier in life in persons with Down syndrome (DS), are presented. The search for biological markers of AD and ways for constrasting its early manifestations are also discussed.

    Citation: Jean A. Rondal. Down syndrome: A curative prospect?[J]. AIMS Neuroscience, 2020, 7(2): 168-193. doi: 10.3934/Neuroscience.2020012

    Related Papers:

  • Experimental work regarding corrective actions on chromosomes and genes, and control of gene products is yielding promising results. It opens the way to advances in dealing with the etiological aspects of Down syndrome and may lead to important changes in the life of individuals affected with this condition. A small number of molecules are being investigated in pharmacological research that may have positive effects on intellectual functioning. Studies of the pathological consequences of the amyloid cascade and the TAU pathology in the etiology of Alzheimer disease (AD), which is more frequent and occuring earlier in life in persons with Down syndrome (DS), are presented. The search for biological markers of AD and ways for constrasting its early manifestations are also discussed.


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    [1] Kalpana V, Ram PVV, Soujanya P, et al. (2017) Robertsonian translocations t(21q;21q) and t(14q;21q) in Down syndrome. Int J Med Health Sci 6: 53-58.
    [2] Asim A, Kumar A, Muthuswamy S, et al. (2015) Down syndrome: an insight of the disease. J Biomed Sci 22: 41-50. doi: 10.1186/s12929-015-0138-y
    [3] Lyle R, Bena F, Gagos S, et al. (2009) Genotype-phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy of chromosome 21. Eur J Hum Genet 17: 454-466. doi: 10.1038/ejhg.2008.214
    [4] Ait Yahya-Graison E, Aubert J, Dauphinot L, et al. (2007) Classification of human chromosome 21 gene-expression variations in Down syndrome: Impact on disease phenotypes. Am J Hum Genet 81: 475-491. doi: 10.1086/520000
    [5] Di Cunto F, Berto G (2013)  Molecular pathways of Down Syndrome Critical Region genes.
    [6] Barlow G, Chen X, Shi Z, et al. (2001) Down syndrome congenital heart disease: A narrowed region and a candidate gene. Genet Med 3: 91-101. doi: 10.1097/00125817-200103000-00002
    [7] Korbel J, Tirosh-Wagner T, Urban A, et al. (2009) The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies. Proc Natl Acad Sci USA 106: 12031-12036. doi: 10.1073/pnas.0813248106
    [8] Antonorakis S, Lyle R, Dermitzakis E, et al. (2004) Chromosome 21 and Down syndrome: from genomics to pathophysiology. Nat Rev Genet 5: 725-738. doi: 10.1038/nrg1448
    [9] Sturgeon X, Le T, Ahmed M, et al. (2012) Pathways to cognitive deficits in Down syndrome. Prog Brain Res 197: 73-100. doi: 10.1016/B978-0-444-54299-1.00005-4
    [10] Pelleri MC, Cicchini E, Locatelli C, et al. (2016) Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.1.3 as critical to the phenotype. Hum Mol Genet 25: 2525-2538.
    [11] Pelleri MC, Cicchini E, Petersen M, et al. (2019) Partial trisomy map: Ten cases further supporting the highly restricted Down syndrome critical region (HR-DSCR) on human chromosome 21. Mol Genet Genomic Med 7: e797. doi: 10.1002/mgg3.797
    [12] Homfray T, Farndon P (2014) Fetal anomalies. The geneticist's approach. Twining's Textbook of Fetal Abnormalities London: Churchill Livingstone, 139-160.
    [13] Rondal JA, Perera J, Spiker D (2011)  Neurocognitive Rehabilitation of Down Syndrome Cambridge: Cambridge University Press. doi: 10.1017/CBO9780511919299
    [14] Chapman R, Hesketh L (2000) Behavioral phenotype of individuals with Down syndrome. Ment Retard Dev Dis Res Rev 6: 84-95. doi: 10.1002/1098-2779(2000)6:2<84::AID-MRDD2>3.0.CO;2-P
    [15] Abbeduto L, Warren S, Conners F (2007) Language development in Down syndrome: from the prelinguistic period to the acquisition of literacy. Ment Retard Dev Dis Res Rev 13: 247-261. doi: 10.1002/mrdd.20158
    [16] Takahashi K, Tanabe K, Ohnuki M, et al. (2007) Induction of pluripotent stem cells from adult human fiboblasts by defined factors. Cell 131: 861-72. doi: 10.1016/j.cell.2007.11.019
    [17] Li L, Chang K, Wang P, et al. (2012) Trisomy correction in Down syndrome induced pluripotent stem cells. Cell Stem Cell 11: 615-619. doi: 10.1016/j.stem.2012.08.004
    [18] Jiang J, Jing Y, Cost G, et al. (2013) Translating dosage compensation for trisomy 21. Nature 500: 296-300. doi: 10.1038/nature12394
    [19] Amano T, Jeffries E, Amano M, et al. (2015) Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures. DNA Res 22: 331-342. doi: 10.1093/dnares/dsv016
    [20] Inoue M, Kajiwara K, Yamaguchi A, et al. (2019) Autonomous trisomic rescue of Down syndrome cells. Lab Invest 99: 885-897. doi: 10.1038/s41374-019-0230-0
    [21] Epstein C (2001) Down syndrome (trisomy 21). The Metabolic and Molecular Bases of Inherited Disease New York: McGraw-Hill, 1223-1256.
    [22] Lejeune J (1990) Pathogenesis of mental deficiency in trisomy 21. Am J Med Genet 37: 20-30. doi: 10.1002/ajmg.1320370705
    [23] Delabar JM, Théophile D, Rahmani Z, et al. (1993) Molecular mapping of twenty-four features of Down syndrome on chromosome 21. Eur J Hum Genet 1: 114-124. doi: 10.1159/000472398
    [24] Tejedor F, Hammerle B (2011) MNB/DYRK1A as a multiple regulator of neuronal development. FEBS J 278: 223-235. doi: 10.1111/j.1742-4658.2010.07954.x
    [25] Thomazeau A, Lasalle O, Lafrati J, et al. (2014) Prefrontal deficits in a murine model overexpressing the Down syndrome candidate gene dyrk1a. J Neurosci 34: 1138-1147. doi: 10.1523/JNEUROSCI.2852-13.2014
    [26] Li S, Qu Z, Haas M, et al. (2016) The HSA21 gene EURL/C21ORF91 controls neurogenesis within the cerebral cortex and is implicated in the pathogenesis of Down syndrome. Sci Rep 6: 29514. doi: 10.1038/srep29514
    [27] Chakrabarti L, Best T, Cramer N, et al. (2010) Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome. Nat Neurosci 13: 927-934. doi: 10.1038/nn.2600
    [28] Manley W, Anderson S (2019) Dosage counts: Correcting trisomy-21-related phenotypes in human organoids and xenografts. Cell Stem Cell 24: 835-36. doi: 10.1016/j.stem.2019.05.009
    [29] Ishihara K, Shimizu R, Takata K, et al. (2019) Perturbation of the immune cells and prenatal neurogenesis by the triplication of the Erg gene in mouse models of Down syndrome. Brain Pathol 30: 75-91. doi: 10.1111/bpa.12758
    [30] Aboudafir E (2017) Trisomie 21: Perspectives Actuelles de Recherche de Traitement. Unpublished doctoral dissertation France: Université de Lorraine, Nancy, Available from: HAL, univ-Lorraine.fr/hal01932163.
    [31] Fillat C, Bofill-De Ros X, Santos M, et al. (2014) Identification de genes clave implicados en el sindrome de Down mediante terapia genetica. Rev Med Int Sindrome Down 18: 21-28. doi: 10.1016/S2171-9748(14)70049-2
    [32] Wang X, Zhao Y, Zhang X, et al. (2013) Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down syndrome. Nature Med 19: 473-480. doi: 10.1038/nm.3117
    [33] Rueda N, Flórez J, Martinez-Cue C (2012) Mouse models of Down syndrome as a tool to unravel the causes of mental disabilities. Neural Plast 2012: 584071. doi: 10.1155/2012/584071
    [34] Aziz N, Guedj F, Pennings J, et al. (2018) Lifespan analysis of brain development, gene expression and behavioral phenotypes in the Ts1Cje, Ts65Dn and Dp(16)1/Yey mouse models of Down syndrome. Dis Mod Mech 11: dmm031013. doi: 10.1242/dmm.031013
    [35] Yu T, Li Z, Jia Z, et al. (2010) A mouse model of Down syndrome trisomic for all human chromosome 21 syntenic regions. Hum Mol Genet 19: 2780-2791. doi: 10.1093/hmg/ddq179
    [36] Xu R, Brawner A, Li S, et al. (2019) OLIG2 drives abnormal neurodevelopmental phenotypes in human iPSC-based organoid and chimeric mouse models of Down syndrome. Cell Stem Cell 24: 908-926.E8. doi: 10.1016/j.stem.2019.04.014
    [37] Caplan A, Wilson J (2000) The clinical challenges of in utero therapy. Nat Genet 24: 107-108. doi: 10.1038/72747
    [38] Nakano-Kobayashi A, Awaya T, Kii I, et al. (2017) Prenatal neurogenesis induction therapy normalizes brain structure and function in Down syndrome mice. Proc Natl Acad Sci USA 114: 10268-10273. doi: 10.1073/pnas.1704143114
    [39] Hibaoui Y, Grad I, Letourneau A, et al. (2014) Modelling and rescuing neurodevelopmental defect of Down syndrome using pluripotent stem cells from monozygotic twins discordant for trisomy 21. EMBO Mol Med 6: 259-277. doi: 10.1002/emmm.201302848
    [40] Guedj F, Sebrie C, Rivals I, et al. (2009) Green tea polyphenols rescue brain defects induced by overexpression of DYRK1A. PloS One 4: 1-8. doi: 10.1371/journal.pone.0004606
    [41] Stagni F, Giacomini A, Emili M, et al. (2016) Short- and long-term effects of neonatal pharmacotherapy with epigallocatechin-3-gallate on hippocampal development in the Ts65Dn mouse model of Down syndrome. Neuroscience 333: 277-301. doi: 10.1016/j.neuroscience.2016.07.031
    [42] De la Torre R, De Sola S, Pons M, et al. (2014) Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in human. Mol Nutr Food Res 58: 278-288. doi: 10.1002/mnfr.201300325
    [43] De la Torre R, De Sola S, Hernandez G, et al. (2016) Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): A double-blind, randomized, placebo-controlled, phase 2 trial. Lancet Neurol 15: 801-810. doi: 10.1016/S1474-4422(16)30034-5
    [44] Xicota L, Rodriguez J, Langohr K, et al. (2020) Effect of epigallocatechin gallate on the body composition and lipid profile of Down syndrome individuals: Implications for clinical management. Clin Nutr 39: 1292-1300. doi: 10.1016/j.clnu.2019.05.028
    [45] Long R, Drawbaugh M, Davis C, et al. (2019) Usage of and attitudes about green tea extract and epigallocathechin-3-gallate (EGCG) as a therapy in individuals with Down syndrome. Complement Ther Med 45: 234-241. doi: 10.1016/j.ctim.2019.07.002
    [46] Sparks A, Truble C, Wang E, et al. (2012) Noninvasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: Evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol 206: 319 e1-e9. doi: 10.1016/j.ajog.2012.01.030
    [47] Nicolaides K, Syngelaki A, Poon L, et al. (2014) First-trimester contingent screening for trisomy 21, 18, and 13 by biomarkers and maternal blood cell-free DNA testing. Fetal Diagn Ther 35: 185-192. doi: 10.1159/000356066
    [48] Sun X, Lu J, Ma X (2019) An efficient method for noninvasive prenatal diagnosis of fetal trisomy 13, trisomy 18, and trisomy 21. PloS One 14: e0215368. doi: 10.1371/journal.pone.0215368
    [49] Shan D, Wang H, Khatri P, et al. (2019) The urinary peptidome as a noninvasive biomarker development strategy for prenatal screening of Down's syndrome. OMICS 23: 439-447. doi: 10.1089/omi.2019.0098
    [50] Reena M, Pisani P, Conversano F, et al. (2013) Sonographic markers for early diagnosis of fetal malformations. World J Radiol 5: 356-371. doi: 10.4329/wjr.v5.i10.356
    [51] Zbucka-Kretowska M, Niemira M, Paczkowska-Abdulasam M, et al. (2019) Prenatal circulating microRNA signatures of foetal Down syndrome. Sci Rep 9: 1-6. doi: 10.1038/s41598-018-35876-5
    [52] Malik S, Vinukonda G, Vose L, et al. (2013) Neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth. J Neurosci 33: 411-423. doi: 10.1523/JNEUROSCI.4445-12.2013
    [53] Gotti S, Caricati E, Panzica G (2011) Alterations of brain circuits in DS murine models. J Chem Neuroanat 42: 317-326. doi: 10.1016/j.jchemneu.2011.09.002
    [54] Chang Q, Gold P (2008) Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome. Neurobiol Learn Mem 89: 167-177. doi: 10.1016/j.nlm.2007.05.007
    [55] Kelley C, Ash J, Powers B, et al. (2016) Effects of maternal choline supplementation on the septohippocampal cholinergic system in the Ts65Dn mouse model of Down syndrome. Curr Alzheimer Res 13: 84-96. doi: 10.2174/1567205012666150921100515
    [56] Heller J, Spiridigliozzi G, Sullivan J, et al. (2003) Donepezil for the treatment of language deficits in adults with Down syndrome: a preliminary 24-week open trial. Am Med Genet 116A: 111-116. doi: 10.1002/ajmg.a.10074
    [57] Heller J, Spiridigliozzi G, Doraiswamy P, et al. (2004) Donepezil effects on language in children with Down syndrome. Results of the first 22-week pilot clinical trial. Am J Med Genet 130A: 325-26. doi: 10.1002/ajmg.a.30184
    [58] Kishnani P, Sommer B, Handen B, et al. (2009) The efficacy, safety, and tolerability of donepezil for the treatment of young adults with Down syndrome. Am J Med Genet 149A: 1641-1654. doi: 10.1002/ajmg.a.32953
    [59] Kishnani P, Heller J, Spiridigliozzi G, et al. (2010) Donepezil for treatment of cognitive dysfunction in children with Down syndrome aged 10–17. Am J Med Genet 152A: 3028-3035. doi: 10.1002/ajmg.a.33730
    [60] Heller J, Spiridigliozzi G, Crissman B, et al. (2006) Safety and efficacy of rivastigmine in adolescents with Down syndrome: A preliminary 20-week, open-label study. J Child Adolesc Psychopharmacol 16: 755-765. doi: 10.1089/cap.2006.16.755
    [61] Heller J, Spiridigliozzi G, Crissman B, et al. (2010) Safety and efficacy of rivastigmine in adolescents with Down syndrome: Long-term follow-up. J Child Adolesc Psychopharmacol 20: 517-520. doi: 10.1089/cap.2009.0099
    [62] Gardiner K (2015) Pharmacological approaches to improving cognitive function in Down syndrome: current status and considerations. Drug Des Devel Ther 9: 103-125.
    [63] Costa A, Scott-McKean J, Stasko M (2008) Acute injections of the NMDA receptor antagonist memantine rescue performance deficits of the Ts65Dn mouse model of Down syndrome on a fear conditioning test. Neuropsychopharmacology 33: 1624-1632. doi: 10.1038/sj.npp.1301535
    [64] Capone G (2011) Pharmacotherapy for children with Down syndrome. Neurocognitive Rehabilitation of Down Syndrome Cambridge: Cambridge University Press, 96-116. doi: 10.1017/CBO9780511919299.008
    [65] Fernandez F, Morishita W, Zuniga E, et al. (2007) Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nat Neurosci 10: 411-413. doi: 10.1038/nn1860
    [66] Liogier d'Ardhuy X, Edgin J, Bouis C, et al. (2015) Assessment of cognitive scales to examine memory, executive function and language in individuals with Down syndrome: Implications of a 6-month observational study. Front Behav Neurosci 9: 300. doi: 10.3389/fnbeh.2015.00300
    [67] Guidi S, Stagni F, Bianchi P, et al. (2014) Prenatal pharmacotherapy rescues brain development in a Down's syndrome mouse model. Brain 137: 380-401. doi: 10.1093/brain/awt340
    [68] Lockrow J, Prakasam A, Huang P, et al. (2009) Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model. Exp Neurol 216: 278-289. doi: 10.1016/j.expneurol.2008.11.021
    [69] Sano M, Aisen P, Andrews H, et al. (2016) Vitamin E in aging persons with Down syndrome: A randomized, placebo-controlled clinical trial. Neurology 86: 2071-2076. doi: 10.1212/WNL.0000000000002714
    [70] Lobaugh N, Karaskov V, Rombough V, et al. (2001) Piracetam therapy does not enhance cognitive functioning in children with Down syndrome. Arch Pediatr Adolesc Med 155: 442-448. doi: 10.1001/archpedi.155.4.442
    [71] Plane J, Chen Y, Pleasure D, et al. (2010) Prospects for minocycline protection. Arch Neurol 67: 1442-1448. doi: 10.1001/archneurol.2010.191
    [72] Chen C, Jiang P, Xue H, et al. (2014) Role of astroglia in Down's syndrome revealed by patient-derived human-induced pluripotent stem cells. Nat Commun 5: 1-18.
    [73] Brose R, Svonenko A, Devenney B, et al. (2019) Hydroxyurea improves spatial memory and cognitive plasticity in mice and has a mild effect on these parameters in a Down syndrome mouse model. Front Aging Neurosci 11: 96. doi: 10.3389/fnagi.2019.00096
    [74] Prasher V (2005)  Alzheimer and Dementia in Down Syndrome and Intellectual Disabilities Abingdon: Radcliffe.
    [75] Doran E, Keator D, Head E, et al. (2017) Down syndrome, partial trisomy, and absence of Alzheimer's disease: The role of APP. J Alzheimers Dis 56: 459-470. doi: 10.3233/JAD-160836
    [76] O'Brien R, Wong P (2011) Amyloid precursor protein processing and Alzheimer's disease. Ann Rev Neurosci 34: 185-204. doi: 10.1146/annurev-neuro-061010-113613
    [77] Rafii M, Lukic A, Andrews R, et al. (2017) PET imaging of Tau pathology and relationship to amyloid, longitudinal MRI, and cognitive change in Down syndrome: Results from the Down Syndrome Biomarker Initiative (DSBI). J Alzheimers Dis 60: 439-450. doi: 10.3233/JAD-170390
    [78] Rafii M (2018) Tau PET for staging of Alzheimer's disease in Down syndrome. Dev Neurobiol 79: 711-715. doi: 10.1002/dneu.22658
    [79] Vogels O (1990)  The Nucleus Basalis of Meynert Complex and Adjacent Structures in Normal Aging and Alzheimer's Disease Nijmegen: Press of the Radbouw University.
    [80] King A, Liu L, Chang R, et al. (2015) Nucleus basalis of Meynert revisited: anatomy, history and differential involvement in Alzheimer's and Parkinson's disease. Acta Neuropathol 129: 527-40. doi: 10.1007/s00401-015-1392-5
    [81] Zhou J, Bingquian L (2013) Alzheimer's disease and prion protein. Intractable Rare Dis Res 2: 35-44.
    [82] Novak P, Prcina M, Kontseva E (2011) Tauons and prions: Infamous cousins? Alzheimer Dis 26: 413-430. doi: 10.3233/JAD-2011-110194
    [83] Hsiung G, Sadovnick A (2007) Genetics and dementia: Risk factors, diagnosis, and management. Alzheimer Dement 3: 418-427. doi: 10.1016/j.jalz.2007.07.010
    [84] Schipper H (2011) Apolipoprotein E: implications for AD neurobiology, epidemiology and risk assessment. Neurobiol Aging 32: 77-90. doi: 10.1016/j.neurobiolaging.2009.04.021
    [85] Raha-Chowdhury R, Henderson J, Raha A, et al. (2019) Choroid plexus acts as gatekeeper for TREM2, abnoremal accumulation of ApoE, and fibrillary Tau in Alzheimer's disease and in Down syndrome dementia. J Alzheimers Dis 69: 91-101. doi: 10.3233/JAD-181179
    [86] Firth N, Startin C, Fisher E, et al. (2018) Aging related cognitive changes associated with Alzheimer's disease in Down syndrome. Ann Clin Transl Neurol 20: 741-751. doi: 10.1002/acn3.571
    [87] Arboleda-Velasquez J, Lopera F, O'Hare M, et al. (2019) Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: A case report. Nat Med 25: 1680-1683. doi: 10.1038/s41591-019-0611-3
    [88] Rogaeva E, Meng Y, Lee J, et al. (2007) The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer's disease. Nat Genet 39: 168-177. doi: 10.1038/ng1943
    [89] Wallon D, Rousseau S, Rovelet-Lecrux A, et al. (2012) The French series of autosomal dominant early onset Alzheimer's disease cases: mutation spectrum and cerebrospinal fluid biomarkers. J Alzheimers Dis 30: 847-856. doi: 10.3233/JAD-2012-120172
    [90] Hochino T, Kamino K, Matsumoto M (2002) Gene dose effect of the APOE-epsilon 4 allele on plasma HDL cholesterol level in patients with Alzheimer's disease. Neurobiol Aging 23: 41-45. doi: 10.1016/S0197-4580(01)00252-4
    [91] Malegiannaki A, Katsarou D, Liolios A, et al. (2019) Ageing and Down syndrome: Neurocognitive characteristics and pharmacological treatment. Hell J Nucl Med 22: 123-132.
    [92] Sanchez M, Heyn S, Das D, et al. (2012) Neurobiological elements of cognitive dysfunction in Down syndrome: Exploring the role of APP. Biol Psychiatry 71: 403-409. doi: 10.1016/j.biopsych.2011.08.016
    [93] Boada R, Hutaff-Lee C, Schrader A, et al. (2012) Antagonism of NMDA receptors as a potential treatment for Down syndrome: A pilot randomized controlled trial. Transl Psychiatry 2: e141. doi: 10.1038/tp.2012.66
    [94] Schenk D, Barbour R, Dunn W, et al. (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400: 173-177. doi: 10.1038/22124
    [95] Matsunaga S, Kishi T, Annes P, et al. (2015) Lithium as a treatment for Alzheiner's disease: A systematic review and meta-analysis. J Alzheimers Dis 48: 403-410. doi: 10.3233/JAD-150437
    [96] Rasore Quartino A (2012) Le terapie attuali per le persone con sindrome di Down: Lo stato del arte. Il Presente Incontra il Futuro. La Sindrome di Down Oggi e Domani Pieve di Cadore: Tiziano, 53-80.
    [97] Sabbagh M (2009) Drug development for Alzheimer's disease: Where are we now and where are we headed? Am J Geriatr Pharmacother 7: 167-185. doi: 10.1016/j.amjopharm.2009.06.003
    [98] Garcia-Cerro S, Rueda N, Vidal L, et al. (2017) Normalizing the gene dosage of DYRK1A in a mouse model of Down syndrome rescues several Alzheimer's disease phenotypes. Neurobiol Dis 106: 76-88. doi: 10.1016/j.nbd.2017.06.010
    [99] Kawakubo T, Mori R, Shirotani N, et al. (2017) Neprilysin is suppressed by dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A) in Down syndrome derived fibroblasts. Biol Pharma Bull 40: 327-333. doi: 10.1248/bpb.b16-00825
    [100] Lee N, Chien Y, Hwu W (2017) A review of biomarkers for Alzheimer's disease in Down syndrome. Neurol Ther 6: 69-81. doi: 10.1007/s40120-017-0071-y
    [101] Hartley S, Handen B, Devenny D, et al. (2017) Cognitive decline and brain amyloid-bêta accumulation across 3 years in adults with Down syndrome. Neurobiol Aging 58: 68-76. doi: 10.1016/j.neurobiolaging.2017.05.019
    [102] Alhajraf F, Ness D, Hye A, et al. (2019) Plasma amyloid and tau as dementia biomarkers in Down syndrome: Systematic review and meta-analysis. Dev Neurobiol 79: 684-698. doi: 10.1002/dneu.22715
    [103] Bik-Multanowsky M, Pietrzyk J, Midro A (2015) MTRNRL12: A candidate blood marker of early Alzheimer's disease-like dementia in adults with Down syndrome. J Alzheimers Dis 46: 145-150. doi: 10.3233/JAD-143030
    [104] Shinomoto M, Kasai T, Tatebe H, et al. (2019) Plasma neurofilament light chain: A potential prognostic biomarker of dementia in adult Down syndrome patients. PloS One 14: e0211575. doi: 10.1371/journal.pone.0211575
    [105] Rafii M, Donohue M, Matthews D, et al. (2019) Plasma neurofilament light and Alzheimer's disease biomarkers in Down syndrome: Results from the Down Syndrome Biomarker Initiative (DSBI). J Alzheimers Dis 70: 131-138. doi: 10.3233/JAD-190322
    [106] Hamlett E, Ledreux A, Potter H, et al. (2018) Exosomal biomarkers in Down syndrome and Alzheimer's disease. Free Radical Biol Medicine 114: 110-121. doi: 10.1016/j.freeradbiomed.2017.08.028
    [107] Motta C, Di Lorenzo F, Ponzo V, et al. (2017) Transcranial magnetic stimulation predicts cognitive decline in patients with Alzheimer's disease. J Neurol Neurosurg Psychiatry 89: 1237-1242. doi: 10.1136/jnnp-2017-317879
    [108] Nawa N, Hirata K, Kawatani K, et al. (2019) Elimination of protein aggregates prevents premature senescence in human trisomy 21 fibroblasts. PloS One 14: e0219592. doi: 10.1371/journal.pone.0219592
    [109] Li JG, Chiu J, Praticò D (2019) Full recovery of Alzheimer's disease phenotype by gain of function of vacuolar protein sorting 35. Mol Psychiatry 1-11.
    [110] Vagnozzi A, Li JG, Chiu J, et al. (2019) VPS35 regulates tau phosphorylation and neuropathology in taupathy. Mol Psychiatry 1-14.
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