A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome (original) (raw)
Lejeune, J., Gautier, M. & Turpin, R. Etude des chromosomes somatiques de neuf enfants mongoliens. C. R. Hebd. Seances Acad. Sci.248, 1721–1722 (in French) (1959). CASPubMed Google Scholar
de Graaf, G., Buckley, F. & Skotko, B. G. Estimates of the live births, natural losses, and elective terminations with Down syndrome in the United States. Am. J. Med. Genet. A167A, 756–767 (2015). PubMed Google Scholar
Wu, J. H. & Morris, J. K. Trends in maternal age distribution and the live birth prevalence of Down's syndrome in England and Wales: 1938–2010. Eur. J. Hum. Genet.21, 943–947 (2013). PubMedPubMed Central Google Scholar
Wu, J. H. & Morris, J. K. The population prevalence of Down's syndrome in England and Wales in 2011. Eur. J. Hum. Genet.21, 1016–1019 (2013). PubMedPubMed Central Google Scholar
Wiseman, F. K., Alford, K. A., Tybulewicz, V. L. J. & Fisher, E. M. C. Down syndrome — recent progress and future prospects. Hum. Mol. Genet.18, R75–R83 (2009). CASPubMedPubMed Central Google Scholar
McCarron, M., McCallion, P., Reilly, E. & Mulryan, N. A prospective 14-year longitudinal follow-up of dementia in persons with Down syndrome. J. Intellect. Disabil. Res.58, 61–70 (2014). CASPubMed Google Scholar
Zigman, W. B., Schupf, N., Urv, T., Zigman, A. & Silverman, W. Incidence and temporal patterns of adaptive behavior change in adults with mental retardation. Am. J. Mental Retard.107, 161–174 (2002). Google Scholar
Hooli, B. V. et al. Role of common and rare APP DNA sequence variants in Alzheimer disease. Neurology78, 1250–1257 (2012). CASPubMedPubMed Central Google Scholar
Kasuga, K. et al. Identification of independent APP locus duplication in Japanese patients with early-onset Alzheimer disease. J. Neurol. Neurosurg. Psychiatry80, 1050–1052 (2009). CASPubMed Google Scholar
McNaughton, D. et al. Duplication of amyloid precursor protein (APP), but not prion protein (PRNP) gene is a significant cause of early onset dementia in a large UK series. Neurobiol. Aging33, 426.e13–426.e21 (2010). Google Scholar
Rovelet-Lecrux, A. et al. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat. Genet.38, 24–26 (2006). CASPubMed Google Scholar
Rovelet-Lecrux, A. et al. APP locus duplication in a Finnish family with dementia and intracerebral haemorrhage. J. Neurol. Neurosurg. Psychiatry78, 1158–1159 (2007). CASPubMedPubMed Central Google Scholar
Sleegers, K. et al. APP duplication is sufficient to cause early onset Alzheimer's dementia with cerebral amyloid angiopathy. Brain129, 2977–2983 (2006). PubMed Google Scholar
Swaminathan, S. et al. Analysis of copy number variation in Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals. PLoS ONE7 e50640 (2012). CASPubMedPubMed Central Google Scholar
Thonberg, H. et al. Mutation screening of patients with Alzheimer disease identifies APP locus duplication in a Swedish patient. BMC Res. Notes4, 476 (2011). CASPubMedPubMed Central Google Scholar
Prasher, V. P. et al. Molecular mapping of Alzheimer-type dementia in Down's syndrome. Ann. Neurol.43, 380–383 (1998). CASPubMed Google Scholar
Korbel, J. O. et al. The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies. Proc. Natl Acad. Sci. USA106, 12031–12036 (2009). CASPubMedPubMed Central Google Scholar
Fraser, J. & Mitchell, A. Kalmuc idiocy: report of a case with autopsy with notes on 62 cases. J. Mental Sci.22, 161–169 (1876). Google Scholar
Strydom, A. et al. Dementia in older adults with intellectual disabilities — epidemiology, presentation, and diagnosis. J. Intellect. Disabil.7, 96–110 (2010). Google Scholar
Tyrrell, J. et al. Dementia in people with Down's syndrome. Int. J. Geriatr. Psychiatry16, 1168–1174 (2001). CASPubMed Google Scholar
Coppus, A. et al. Dementia and mortality in persons with Down's syndrome. J. Intellect. Disabil. Res.50, 768–777 (2006). CASPubMed Google Scholar
Visser, F. E., Aldenkamp, A. P., vanHuffelen, A. C., Kuilman, M. & Overweg, J. Prospective study of the prevalence of Alzheimer-type dementia in institutionalized individuals with Down syndrome. Am. J. Mental Retard.101, 400–412 (1997). CAS Google Scholar
Krinsky-McHale, S. J. et al. Successful aging in a 70-year-old man with Down syndrome: a case study. Intellect. Dev. Disabil.46, 215–228 (2008). PubMed Google Scholar
Coppus, A. M. W. et al. Early age at menopause is associated with increased risk of Dementia and mortality in women with Down syndrome. J. Alzheimers Dis.19, 545–550 (2010). PubMed Google Scholar
Schupf, N. et al. Onset of dementia is associated with age at menopause in women with Down's syndrome. Ann. Neurol.54, 433–438 (2003). PubMed Google Scholar
Cosgrave, M. P., Tyrrell, J., McCarron, M., Gill, M. & Lawlor, B. A. Age at onset of dementia and age of menopause in women with Down's syndrome. J. Intellect. Disabil. Res.43, 461–465 (1999). PubMed Google Scholar
Draheim, C. C., Geijer, J. R. & Dengel, D. R. Comparison of intima-media thickness of the carotid artery and cardiovascular disease risk factors in adults with versus without the Down syndrome. Am. J. Cardiol.106, 1512–1516 (2010). PubMed Google Scholar
Zigman, W. B. et al. Cholesterol level, statin use and Alzheimer's disease in adults with Down syndrome. Neurosci. Lett.416, 279–284 (2007). CASPubMedPubMed Central Google Scholar
Ylaherttuala, S., Luoma, J., Nikkari, T. & Kivimaki, T. Downs-syndrome and atherosclerosis. Atherosclerosis76, 269–272 (1989). CAS Google Scholar
van de Louw, J., Vorstenbosch, R., Vinck, L., Penning, C. & Evenhuis, H. Prevalence of hypertension in adults with intellectual disability in the Netherlands. J. Intellect. Disabil. Res.53, 78–84 (2009). CASPubMed Google Scholar
Stampfer, M. J. Cardiovascular disease and Alzheimer's disease: common links. J. Internal Med.260, 211–223 (2006). CASPubMed Google Scholar
Zigman, W. B. et al. Alzheimer's disease in adults with Down syndrome. Int. Rev. Res. Ment. Retard.36, 103–145 (2008). PubMedPubMed Central Google Scholar
Margallo-Lana, M. L. et al. Fifteen-year follow-up of 92 hospitalized adults with Down's syndrome: incidence of cognitive decline, its relationship to age and neuropathology. J. Intellect. Disabil. Res.51, 463–477 (2007). CASPubMed Google Scholar
Devenny, D. A., Krinsky-McHale, S. J., Sersen, G. & Silverman, W. P. Sequence of cognitive decline in dementia in adults with Down's syndrome. J. Intellect. Disabil. Res.44, 654–665 (2000). PubMed Google Scholar
Devenny, D. A., Zimmerli, E. J., Kittler, P. & Krinsky-McHale, S. J. Cued recall in early-stage dementia in adults with Down's syndrome. J. Intellect. Disabil. Res.46, 472–483 (2002). CASPubMed Google Scholar
Krinsky-McHale, S. J., Devenny, D. A. & Silverman, W. P. Changes in explicit memory associated with early dementia in adults with Down's syndrome. J. Intellect. Disabil. Res.46, 198–208 (2002). CASPubMed Google Scholar
Adams, D. & Oliver, C. The relationship between acquired impairments of executive function and behaviour change in adults with Down syndrome. J. Intellect. Disabil. Res.54, 393–405 (2010). CASPubMed Google Scholar
Ball, S. L. et al. Personality and behaviour changes mark the early stages of Alzheimer's disease in adults with Down's syndrome: findings from a prospective population-based study. Int. J. Geriatr. Psychiatry21, 661–673 (2006). PubMed Google Scholar
Ball, S. L., Holland, A. J., Treppner, P., Watson, P. C. & Huppert, F. A. Executive dysfunction and its association with personality and behaviour changes in the development of Alzheimer's disease in adults with Down syndrome and mild to moderate learning disabilities. Br. J. Clin. Psychol.47, 1–29 (2008). PubMed Google Scholar
Holland, A. J., Hon, J., Huppert, F. A. & Stevens, F. Incidence and course of dementia in people with Down's syndrome: findings from a population-based study. J. Intellect. Disabil. Res.44, 138–146 (2000). PubMed Google Scholar
Oliver, C., Kalsy, S., McQuillan, S. & Hall, S. Behavioural excesses and deficits associated with dementia in adults who have Down syndrome. J. Appl. Res. Intellect. Disabil.24, 208–216 (2011). Google Scholar
Nelson, L. D., Orme, D., Osann, K. & Lott, I. T. Neurological changes and emotional functioning in adults with Down Syndrome. J. Intellect. Disabil. Res.45, 450–456 (2001). CASPubMed Google Scholar
Powell, D. et al. Frontal white matter integrity in adults with Down syndrome with and without dementia. Neurobiol. Aging35, 1562–1569 (2014). PubMedPubMed Central Google Scholar
Jennings, D. et al. Age dependence of brain ß-amyloid deposition in Down syndrome: an [18F]florbetaben PET study. Neurology84, 500–507 (2015). CASPubMed Google Scholar
Masters, M. C., Morris, J. C. & Roe, C. M. 'Noncognitive' symptoms of early Alzheimer disease: a longitudinal analysis. Neurology84, 617–622 (2015). CASPubMedPubMed Central Google Scholar
Wallon, D. et al. The French series of autosomal dominant early onset Alzheimer's disease cases: mutation spectrum and cerebrospinal fluid biomarkers. J. Alzheimers Dis.30, 847–856 (2012). CASPubMed Google Scholar
De Simone, R., Puig, X. S., Gélisse, P., Crespel, A. & Genton, P. Senile myoclonic epilepsy: delineation of a common condition associated with Alzheimer's disease in Down syndrome. Seizure19, 383–389 (2010). PubMed Google Scholar
Moller, J. C., Hamer, H. M., Oertel, W. H. & Rosenow, F. Late-onset myoclonic epilepsy in Down's syndrome (LOMEDS). Seizure10, 303–305 (2001). CASPubMed Google Scholar
d'Orsi, G. & Specchio, L. M. Progressive myoclonus epilepsy in Down syndrome patients with dementia. J. Neurol.261, 1584–1597 (2014). CASPubMed Google Scholar
Friedman, D., Honig, L. S. & Scarmeas, N. Seizures and epilepsy in Alzheimer's disease. CNS Neurosci. Ther.18, 285–294 (2012). PubMed Google Scholar
Vossel, K. A. et al. Seizures and epileptiform activity in the early stages of Alzheimer disease. JAMA Neurol.70, 1158–1166 (2013). PubMedPubMed Central Google Scholar
Irizarry, M. C. et al. Incidence of new-onset seizures in mild to moderate Alzheimer disease. Arch. Neurol.69, 368–372 (2012). PubMedPubMed Central Google Scholar
Lott, I. T. et al. Down syndrome and dementia: seizures and cognitive decline. J. Alzheimers Dis.29, 177–185 (2012). PubMedPubMed Central Google Scholar
Crayton, L., Oliver, C., Holland, A., Bradbury, J. & Hall, S. The neuropsychological assessment of age related cognitive deficits in adults with Down's syndrome. J. Appl. Res. Intellect. Disabil.11, 255–272 (1998). Google Scholar
Dalton, A. J., Mehta, P. D., Fedor, B. L. & Patti, P. J. Cognitive changes in memory precede those in praxis in aging persons with Down syndrome. J. Intellect. Dev. Disabil.24, 169–187 (1999). Google Scholar
Struwe, F. Histopathologische Untersuchungen über Entstehung und Wesen der senile Plaques. Z. Gesamte Neurol. Psy.122, 291–307 (in German) (1929). Google Scholar
Glenner, G. G. & Wong, C. W. Alzheimer's disease and Downs syndrome — sharing of a unique cerebrovascular amyloid fibril protein. Biochem. Biophys. Res. Commun.122, 1131–1135 (1984). CASPubMed Google Scholar
Goate, A. et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature349, 704–706 (1991). CASPubMed Google Scholar
Hardy, J. A. & Higgins, G. A. Alzheimer's disease — the amyloid cascade hypothesis. Science256, 184–185 (1992). CASPubMed Google Scholar
Goedert, M., Spillantini, M. G., Cairns, N. J. & Crowther, R. A. Tau proteins of Alzheimer paired helical filaments — abnormal phosphorylation of all 6 brain isoforms. Neuron8, 159–168 (1992). CASPubMed Google Scholar
Mann, D. M. A. Alzheimer's disease and Down's syndrome. Histopathology13, 125–137 (1988). CASPubMed Google Scholar
Wisniewski, H. M. & Rabe, A. Discrepancy between Alzheimer-type neuropathology and dementia in persons with Down's syndrome. Ann. NY Acad. Sci.477, 247–260 (1986). CASPubMed Google Scholar
Mann, D. M. A. The pathological association between Down syndrome and Alzheimer's disease. Mech. Ageing Dev.43, 99–136 (1988). CASPubMed Google Scholar
Leverenz, J. B. & Raskind, M. A. Early amyloid deposition in the medial temporal lobe of young Down syndrome patients: a regional quantitative analysis. Exp. Neurol.150, 296–304 (1998). CASPubMed Google Scholar
Braak, H. & Braak, E. Neuropathological staging of Alzheimer-related changes. Acta Neuropathol.82, 239–259 (1991). CASPubMed Google Scholar
Egensperger, R. et al. Reverse relationship between β-amyloid precursor protein and beta-amyloid peptide plaques in Down's syndrome versus sporadic/familial Alzheimer's disease. Acta Neuropathol.97, 113–118 (1999). CASPubMed Google Scholar
Mann, D. M. A., Yates, P. O., Marcyniuk, B. & Ravindra, C. R. Loss of neurons from cortical and subcortical areas in Down's syndrome patients at middle-age — quantitative comparisons with younger Down's patients and patients with Alzheimer's disease. J. Neurol. Sci.80, 79–89 (1987). CASPubMed Google Scholar
Allsop, D., Kidd, M., Landon, M. & Tomlinson, A. Isolated senile plaque cores in Alzheimer's disease and Down's syndrome show differences in morphology. J. Neurol. Neurosurg. Psychiatry49, 886–892 (1986). CASPubMedPubMed Central Google Scholar
Armstrong, R. A. Size frequency distributions of β-amyloid (4β) deposits: a comparative study of four neurodegenerative disorders. Folia Neuropathol.50, 240–249 (2012). CASPubMed Google Scholar
Bero, A. W. et al. Neuronal activity regulates the regional vulnerability to amyloid-β deposition. Nat. Neurosci.14, 750–756 (2011). CASPubMedPubMed Central Google Scholar
Gyure, K. A., Durham, R., Stewart, W. F., Smialek, J. E. & Troncoso, J. C. Intraneuronal Aβ-amyloid precedes development of amyloid plaques in Down syndrome. Arch. Pathol. Lab. Med.125, 489–492 (2001). CASPubMed Google Scholar
Hirayama, A., Horikoshi, Y., Maeda, M., Ito, M. & Takashima, S. Characteristic developmental expression of amyloid β40, 42 and 43 in patients with Down syndrome. Brain Dev.25, 180–185 (2003). PubMed Google Scholar
Iwatsubo, T., Mann, D. M. A., Odaka, A., Suzuki, N. & Ihara, Y. Amyloid β protein (Aβ) deposition: Aβ42(43) precedes Aβ40 in Down syndrome. Ann. Neurol.37, 294–299 (1995). CASPubMed Google Scholar
Mori, C. et al. Intraneuronal Aβ42 accumulation in Down syndrome brain. Amyloid9, 88–102 (2002). CASPubMed Google Scholar
Wegiel, J. et al. Intraneuronal Aβ immunoreactivity is not a predictor of brain amyloidosis-β or neurofibrillary degeneration. Acta Neuropathol.113, 389–402 (2007). CASPubMedPubMed Central Google Scholar
Wisniewski, K. E., Wisniewski, H. M. & Wen, G. Y. Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann. Neurol.17, 278–282 (1985). CASPubMed Google Scholar
Wisniewski, K. E., Dalton, A. J., Mclachlan, D. R. C., Wen, G. Y. & Wisniewski, H. M. Alzheimer's disease in Down's syndrome: clinicopathologic studies. Neurology35, 957–961 (1985). CASPubMed Google Scholar
Burger, P. C. & Vogel, F. S. The development of pathologic changes of Alzheimer's disease and senile dementia in patients with Down's syndrome. Am. J. Pathol.73, 457–476 (1973). CASPubMedPubMed Central Google Scholar
Lemere, C. A. et al. Sequence of deposition of heterogeneous amyloid β-peptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation. Neurobiol. Dis.3, 16–32 (1996). CASPubMed Google Scholar
Ball, M. J. & Nuttall, K. Neurofibrillary tangles, granulovacuolar degeneration, and neuron loss in Down syndrome: quantitative comparison with Alzheimer dementia. Ann. Neurol.7, 462–465 (1980). CASPubMed Google Scholar
Mann, D. M. A. & Esiri, M. M. The pattern of acquisition of plaques and tangles in the brains of patients under 50 years of age with Down's syndrome. J. Neurol. Sci.89, 169–179 (1989). CASPubMed Google Scholar
Whalley, L. J. The dementia of Down's syndrome and its relevance to etiological studies of Alzheimer's disease. Ann. NY Acad. Sci.396, 39–53 (1982). CASPubMed Google Scholar
Ropper, A. H. & Williams, R. S. Relationship between plaques, tangles, and dementia in Down syndrome. Neurology30, 639–644 (1980). CASPubMed Google Scholar
Godridge, H., Reynolds, G. P., Czudek, C., Calcutt, N. A. & Benton, M. Alzheimer-like neurotransmitter deficits in adult Down's syndrome brain tissue. J. Neurol. Neurosurg. Psychiatry50, 775–778 (1987). CASPubMedPubMed Central Google Scholar
Murphy, G. M. et al. Antigenic profile of plaques and neurofibrillary tangles in the amygdala in Down's syndrome: a comparison with Alzheimer's disease. Brain Res.537, 102–108 (1990). CASPubMed Google Scholar
Motte, J. & Williams, R. S. Age-related-changes in the density and morphology of plaques and neurofibrillary tangles in Down syndrome brain. Acta Neuropathol.77, 535–546 (1989). CASPubMed Google Scholar
Head, E. et al. Parallel compensatory and pathological events associated with Tau pathology in middle aged individuals with Down syndrome. J. Neuropathol. Exp. Neurol.62, 917–926 (2003). CASPubMed Google Scholar
Serrano-Pozo, A., Frosch, M. P., Masliah, E. & Hyman, B. T. Neuropathological alterations in Alzheimer disease. Cold Spring Harb. Perspect. Med.1, a006189 (2011). PubMedPubMed Central Google Scholar
Mann, D. M. A. Cerebral amyloidosis, aging and Alzheimer's disease: a contribution from studies on Down's syndrome. Neurobiol. Aging10, 397–399 (1989). CASPubMed Google Scholar
Evenhuis, H. M. The natural history of dementia in Down's syndrome. Arch. Neurol.47, 263–267 (1990). CASPubMed Google Scholar
McCarron, M. O., Nicoll, J. A. R. & Graham, D. I. A quartet of Down's syndrome, Alzheimer's disease, cerebral amyloid angiopathy, and cerebral haemorrhage: interacting genetic risk factors. J. Neurol. Neurosurg. Psychiatry65, 405–406 (1998). CASPubMedPubMed Central Google Scholar
Mendel, T., Bertrand, E., Szpak, G. M., Stepien, T. & Wierzba-Bobrowicz, T. Cerebral amyloid angiopathy as a cause of an extensive brain hemorrhage in adult patient with Down's syndrome — a case report. Folia Neuropathol.48, 206–211 (2010). PubMed Google Scholar
Naito, K. S., Sekijima, Y. & Ikeda, S. I. Cerebral amyloid angiopathy-related hemorrhage in a middle-aged patient with Down's syndrome. Amyloid15, 275–277 (2008). CASPubMed Google Scholar
Donahue, J. E., Khurana, J. S. & Adelman, L. S. Intracerebral hemorrhage in two patients with Down's syndrome and cerebral amyloid angiopathy. Acta Neuropathol.95, 213–216 (1998). CASPubMed Google Scholar
Handen, B. L. et al. Imaging brain amyloid in nondemented young adults with Down syndrome using Pittsburgh compound B. Alzheimers Dement.8, 496–501 (2012). CASPubMedPubMed Central Google Scholar
Nelson, L. D. et al. Positron emission tomography of brain β-amyloid and Tau levels in adults with Down syndrome. Arch. Neurol.68, 768–774 (2011). PubMedPubMed Central Google Scholar
Matveev, S. V. et al. A distinct subfraction of Aβ is responsible for the high-affinity Pittsburgh compound B-binding site in Alzheimer's disease brain. J. Neurochem.131, 356–368 (2014). CASPubMedPubMed Central Google Scholar
Hartley, S. L. et al. Cognitive functioning in relation to brain amyloid-β in healthy adults with Down syndrome. Brain137, 2556–2563 (2014). PubMedPubMed Central Google Scholar
Landt, J. et al. Using positron emission tomography and carbon 11-labeled Pittsburgh compound B to image brain fibrillar β-amyloid in adults with Down syndrome safety, acceptability, and feasibility. Arch. Neurol.68, 890–896 (2011). PubMed Google Scholar
Lippa, C. F. et al. Transactive response DNA-binding protein 43 burden in familial Alzheimer disease and Down syndrome. Arch. Neurol.66, 1483–1488 (2009). PubMedPubMed Central Google Scholar
Davidson, Y. S. et al. TDP-43 pathological changes in early onset familial and sporadic Alzheimer's disease, late onset Alzheimer's disease and Down's syndrome: association with age, hippocampal sclerosis and clinical phenotype. Acta Neuropathol.122, 703–713 (2011). PubMed Google Scholar
Gibb, W. R. G., Mountjoy, C. Q., Mann, D. M. A. & Lees, A. J. A pathological study of the association between Lewy body disease and Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry52, 701–708 (1989). CASPubMedPubMed Central Google Scholar
Prasher, V. P., Airuehia, E. & Carey, M. The first confirmed case of Down syndrome with dementia with Lewy bodies. J. Appl. Res. Intellect. Disabil.23, 296–300 (2010). Google Scholar
Cataldo, A. M. et al. Aβ localization in abnormal endosomes: association with earliest Aβ elevations in AD and Down syndrome. Neurobiol. Aging25, 1263–1272 (2004). CASPubMed Google Scholar
Lambert, J. C. et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat. Genet.45, 1452–1458 (2013). CASPubMedPubMed Central Google Scholar
Hooli, B. V. et al. Rare autosomal copy number variations in early-onset familial Alzheimer's disease. Mol. Psychiatry19, 676–681 (2014). CASPubMed Google Scholar
Llado, A. et al. Large APP locus duplication in a sporadic case of cerebral haemorrhage. Neurogenetics15, 145–149 (2014). PubMed Google Scholar
Cabrejo, L. et al. Phenotype associated with APP duplication in five families. Brain129, 2966–2976 (2006). PubMed Google Scholar
Noebels, J. A perfect storm: converging paths of epilepsy and Alzheimer's dementia intersect in the hippocampal formation. Epilepsia52, 39–46 (2011). PubMedPubMed Central Google Scholar
Vilardell, M. et al. Meta-analysis of heterogeneous Down syndrome data reveals consistent genome-wide dosage effects related to neurological processes. BMC Genomics12, 229 (2011). PubMedPubMed Central Google Scholar
Letourneau, A. et al. Domains of genome-wide gene expression dysregulation in Down's syndrome. Nature508, 345–350 (2014). CASPubMed Google Scholar
Cheon, M. S., Dierssen, M., Kim, S. H. & Lubec, G. Protein expression of BACE1, BACE2 and APP in Down syndrome brains. Amino Acids35, 339–343 (2008). CASPubMed Google Scholar
Choi, J. H. K. et al. Age-dependent dysregulation of brain amyloid precursor protein in the Ts65Dn Down syndrome mouse model. J. Neurochem.110, 1818–1827 (2009). CASPubMedPubMed Central Google Scholar
Seo, H. & Isacson, O. Abnormal APP, cholinergic and cognitive function in Ts65Dn Down's model mice. Exp. Neurol.193, 469–480 (2005). CASPubMed Google Scholar
Teller, J. K. et al. Presence of soluble amyloid β-peptide precedes amyloid plaque formation in Down's syndrome. Nat. Med.2, 93–95 (1996). CASPubMed Google Scholar
Busciglio, J. et al. Altered metabolism of the amyloid β precursor protein is associated with mitochondrial dysfunction in Down's syndrome. Neuron33, 677–688 (2002). CASPubMed Google Scholar
Govoni, S. et al. Fibroblasts of patients affected by Down's syndrome oversecrete amyloid precursor protein and are hyporesponsive to protein kinase C stimulation. Neurology47, 1069–1075 (1996). CASPubMed Google Scholar
Murray, A., Letourneau, A. & Canzonetta, C. Isogenic induced pluripotent stem cell lines from an adult with mosaic Down syndrome model accelerated neuronal ageing and neurodegeneration. Stem Cells33, 2077–2084 (2015). CASPubMedPubMed Central Google Scholar
Shi, Y. C. et al. A human stem cell model of early Alzheimer's disease pathology in Down syndrome. Sci. Transl. Med.4, 124ra29 (2012). PubMedPubMed Central Google Scholar
Wolvetang, E. W. et al. The chromosome 21 transcription factor ETS2 transactivates the β-APP promoter: implications for Down syndrome. Biochim. Biophys. Acta1628, 105–110 (2003). CASPubMed Google Scholar
Dorval, V., Mazzella, M. J., Mathews, P. M., Hay, R. T. & Fraser, P. E. Modulation of Aβ generation by small ubiquitin-like modifiers does not require conjugation to target proteins. Biochem. J.404, 309–316 (2007). CASPubMedPubMed Central Google Scholar
Li, Y. H. et al. Positive and negative regulation of APP amyloidogenesis by sumoylation. Proc. Natl Acad. Sci. USA100, 259–264 (2003). CASPubMed Google Scholar
Ryoo, S. R. et al. Dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A-mediated phosphorylation of amyloid precursor protein: evidence for a functional link between Down syndrome and Alzheimer's disease. J. Neurochem.104, 1333–1344 (2008). CASPubMed Google Scholar
Wang, X. et al. Sorting nexin 27 regulates Aβ production through modulating γ-secretase activity. Cell Rep.9, 1023–1033 (2014). CASPubMedPubMed Central Google Scholar
Mok, K. Y. et al. Polymorphisms in BACE2 may affect the age of onset Alzheimer's dementia in Down syndrome. Neurobiol. Aging35, 1513.e1–1513.e5 (2014). CAS Google Scholar
Sun, X. L., He, G. Q. & Song, W. H. BACE2, as a novel APP θ-secretase, is not responsible for the pathogenesis of Alzheimer's disease in Down syndrome. FASEB J.20, 1369–1376 (2006). CASPubMed Google Scholar
Azkona, G., Levannon, D., Groner, Y. & Dierssen, M. In vivo effects of APP are not exacerbated by BACE2 co-overexpression: behavioural characterization of a double transgenic mouse model. Amino Acids39, 1571–1580 (2010). CASPubMed Google Scholar
Holler, C. J. et al. BACE2 expression increases in human neurodegenerative disease. Am. J. Pathol.180, 337–350 (2012). CASPubMedPubMed Central Google Scholar
Patel, A. et al. Association of variants within APOE, SORL1, RUNX1, BACE1 and ALDH18A1 with dementia in Alzheimer's disease in subjects with Down syndrome. Neurosci. Lett.487, 144–148 (2011). CASPubMed Google Scholar
Prasher, V. P. et al. Significant effect of APOE epsilon 4 genotype on the risk of dementia in Alzheimer's disease and mortality in persons with Down syndrome. Int. J. Geriatr. Psychiatry23, 1134–1140 (2008). CASPubMedPubMed Central Google Scholar
Deb, S. et al. APOE epsilon 4 influences the manifestation of Alzheimer's disease in adults with Down's syndrome. Br. J. Psychiatry176, 468–472 (2000). CASPubMed Google Scholar
Coppus, A. M. W. et al. The impact of apolipoprotein E on dementia in persons with Down's syndrome. Neurobiol. Aging29, 828–835 (2008). CASPubMed Google Scholar
Schupf, N. et al. Onset of dementia is associated with apolipoprotein E epsilon 4 in Down's syndrome. Ann. Neurol.40, 799–801 (1996). CASPubMed Google Scholar
Hyman, B. T. et al. Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome). Proc. Natl Acad. Sci. USA92, 3586–3590 (1995). CASPubMedPubMed Central Google Scholar
Royston, M. C. et al. Apolipoprotein-e epsilon-2 allele promotes longevity and protects patients with Down's syndrome from dementia. Neuroreport5, 2583–2585 (1994). CASPubMed Google Scholar
Jones, E. L. et al. Evidence that PICALM affects age at onset of Alzheimer's dementia in Down syndrome. Neurobiol. Aging34, 2441.e1–2441.e5 (2013). CAS Google Scholar
Lee, J. H. et al. Association between genetic variants in sortilin-related receptor 1 (SORL1) and Alzheimer's disease in adults with Down syndrome. Neurosci. Lett.425, 105–109 (2007). CASPubMedPubMed Central Google Scholar
Salehi, A. et al. Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron51, 29–42 (2006). CASPubMed Google Scholar
Torroja, L., Chu, H., Kotovsky, I. & White, K. Neuronal overexpression of APPL, the Drosophila homologue of the amyloid precursor protein (APP), disrupts axonal transport. Curr. Biol.9, 489–492 (1999). CASPubMed Google Scholar
Jiang, Y. et al. Alzheimer's-related endosome dysfunction in Down syndrome is Aβ-independent but requires APP and is reversed by BACE-1 inhibition. Proc. Natl Acad. Sci. USA107, 1630–1635 (2010). CASPubMed Google Scholar
Barbosa, S., Pratte, D., Schwarz, H., Pipkorn, R. & Singer-Kruger, B. Oligomeric Dop1p is part of the endosomal Neo1p–Ysl2p–Arl1p membrane remodeling complex. Traffic11, 1092–1106 (2010). CASPubMed Google Scholar
Swaminathan, S. et al. Analysis of copy number variation in Alzheimer's disease: the NIA-LOAD/NCRAD family study. Curr. Alzheimer Res.9, 801–814 (2012). CASPubMedPubMed Central Google Scholar
Chapman, J. et al. A genome-wide study shows a limited contribution of rare copy number variants to Alzheimer's disease risk. Hum. Mol. Genet.22, 816–824 (2013). CASPubMed Google Scholar
Yang, D. S. et al. Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits. Brain134, 258–277 (2011). PubMed Google Scholar
Cossec, J. C. et al. Trisomy for synaptojanin1 in Down syndrome is functionally linked to the enlargement of early endosomes. Hum. Mol. Genet.21, 3156–3172 (2012). CASPubMedPubMed Central Google Scholar
McIntire, L. B. J. et al. Reduction of synaptojanin 1 ameliorates synaptic and behavioral impairments in a mouse model of Alzheimer's disease. J. Neurosci.32, 15271–15276 (2012). CASPubMedPubMed Central Google Scholar
Zhu, L. et al. Reduction of synaptojanin 1 accelerates Aβ clearance and attenuates cognitive deterioration in an Alzheimer mouse model. J. Biol. Chem.288, 32050–32063 (2013). CASPubMedPubMed Central Google Scholar
Busciglio, J. & Yankner, B. A. Apoptosis and increased generation of reactive oxygen species in Down's syndrome neurons in vitro. Nature378, 776–779 (1995). CASPubMed Google Scholar
Shukkur, E. A. et al. Mitochondrial dysfunction and tau hyperphosphorylation in Ts1Cje, a mouse model for Down syndrome. Hum. Mol. Genet.15, 2752–2762 (2006). CASPubMed Google Scholar
Phillips, A. C. et al. Defective mitochondrial function in vivo in skeletal muscle in adults with Down's syndrome: a 31P-MRS study. PLoS ONE8, e84031 (2013). PubMedPubMed Central Google Scholar
Weick, J. P. et al. Deficits in human trisomy 21 iPSCs and neurons. Proc. Natl Acad. Sci. USA110, 9962–9967 (2013). CASPubMedPubMed Central Google Scholar
Zigman, W. B. Atypical aging in Down syndrome. Dev. Disabil. Res. Rev.18, 51–67 (2013). PubMed Google Scholar
Picard, M. & Mcewen, B. S. Mitochondria impact brain function and cognition. Proc. Natl Acad. Sci. USA111, 7–8 (2014). CASPubMed Google Scholar
Lott, I. T. et al. Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation. Am. J. Med. Genet. A155A, 1939–1948 (2011). PubMedPubMed Central Google Scholar
Carlson, G. A. et al. Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice. Hum. Mol. Genet.6, 1951–1959 (1997). CASPubMed Google Scholar
Murakami, K. et al. SOD1 (copper/zinc superoxide dismutase) deficiency drives amyloid β protein oligomerization and memory loss in mouse model of Alzheimer disease. J. Biol. Chem.286, 44557–44568 (2011). CASPubMedPubMed Central Google Scholar
Zis, P., Dickinson, M., Shende, S., Walker, Z. & Strydom, A. Oxidative stress and memory decline in adults with Down syndrome: longitudinal study. J. Alzheimers Dis.31, 277–283 (2012). CASPubMed Google Scholar
deHaan, J. B. et al. Elevation in the ratio of Cu/Zn-superoxide dismutase to glutathione peroxidase activity induces features of cellular senescence and this effect is mediated by hydrogen peroxide. Hum. Mol. Genet.5, 283–292 (1996). CAS Google Scholar
Belichenko, P. V. et al. Excitatory-inhibitory relationship in the fascia dentata in the Ts65Dn mouse model of down syndrome. J. Comp. Neurol.512, 453–466 (2008). Google Scholar
Fernandez, F. et al. Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nat. Neurosci.10, 411–413 (2007). CASPubMed Google Scholar
Schmidt-Sidor, B., Wisniewski, K. E., Shepard, T. H. & Sersen, E. A. Brain growth in Down syndrome subjects 15 to 22 weeks of gestational age and birth to 60 months. Clin. Neuropathol.9, 181–190 (1990). CASPubMed Google Scholar
Takashima, S., Becker, L. E., Armstrong, D. L. & Chan, F. Abnormal neuronal development in the visual cortex of the human fetus and infant with down's syndrome. A quantitative and qualitative Golgi study. Brain Res.225, 1–21 (1981). CASPubMed Google Scholar
Canzonetta, C. et al. DYRK1A-dosage imbalance perturbs NRSF/REST levels, deregulating pluripotency and embryonic stem cell fate in Down syndrome. Am. J. Hum. Genet.83, 388–400 (2008). CASPubMedPubMed Central Google Scholar
Hibaoui, Y. et al. Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21. EMBO Mol. Med.6, 259–277 (2014). CASPubMed Google Scholar
Chang, K. T. & Min, K. T. Upregulation of three Drosophila homologs of human chromosome 21 genes alters synaptic function: implications for Down syndrome. Proc. Natl Acad. Sci. USA106, 17117–17122 (2009). CASPubMedPubMed Central Google Scholar
Cvetkovska, V., Hibbert, A. D., Emran, F. & Chen, B. E. Overexpression of Down syndrome cell adhesion molecule impairs precise synaptic targeting. Nat. Neurosci.16, 677–682 (2013). CASPubMedPubMed Central Google Scholar
Wang, B. P. et al. The amyloid precursor protein controls adult hippocampal neurogenesis through GABAergic interneurons. J. Neurosci.34, 13314–13325 (2014). CASPubMedPubMed Central Google Scholar
Nicolas, M. & Hassan, B. A. Amyloid precursor protein and neural development. Development141, 2543–2548 (2014). CASPubMed Google Scholar
Ma'ayan, A., Gardiner, K. J. & Iyengar, R. The cognitive phenotype of Down syndrome: insights from intracellular network analysis. NeuroRx3, 396–406 (2006). PubMedPubMed Central Google Scholar
Drewes, G. et al. Dephosphorylation of Tau-protein and Alzheimer paired helical filaments by calcineurin and phosphatase-2A. Febs Lett.336, 425–432 (1993). CASPubMed Google Scholar
Liu, F. et al. Overexpression of Dyrk1A contributes to neurofibrillary degeneration in Down syndrome. FASEB J.22, 3224–3233 (2008). CASPubMedPubMed Central Google Scholar
Woods, Y. L. et al. The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bepsilon at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase. Biochem. J.355, 609–615 (2001). CASPubMedPubMed Central Google Scholar
Dowjat, W. K. et al. Trisomy-driven overexpression of DYRK1A kinase in the brain of subjects with Down syndrome. Neurosci. Lett.413, 77–81 (2007). CASPubMed Google Scholar
Shi, J. et al. Increased dosage of Dyrk1A alters alternative splicing factor (ASF)-regulated alternative splicing of Tau in Down syndrome. J. Biol. Chem.283, 28660–28669 (2008). CASPubMedPubMed Central Google Scholar
Wegiel, J. et al. Link between DYRK1A overexpression and several-fold enhancement of neurofibrillary degeneration with 3-repeat Tau protein in Down syndrome. J. Neuropathol. Exp. Neurol.70, 36–50 (2011). CASPubMed Google Scholar
Moore, S. et al. APP metabolism regulates Tau protestasis in human cerebral cortex neurons. Cell Rep.11, 689–696 (2015). CASPubMedPubMed Central Google Scholar
Kimura, R. et al. The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between β-amyloid production and tau phosphorylation in Alzheimer disease. Hum. Mol. Genet.16, 15–23 (2007). CASPubMed Google Scholar
Vazquez-Higuera, J. L. et al. DYRK1A genetic variants are not linked to Alzheimer's disease in a Spanish case-control cohort. BMC Med. Genet.10, 129 (2009). PubMedPubMed Central Google Scholar
Cooper, S. A. et al. Toward onset prevention of cognitive decline in adults with Down syndrome (the TOP-COG study): study protocol for a randomized controlled trial. Trials15, 202 (2014). PubMedPubMed Central Google Scholar
Kim, W. S. et al. Role of ABCG1 and ABCA1 in regulation of neuronal cholesterol efflux to apolipoprotein E discs and suppression of amyloid-β peptide generation. J. Biol. Chem.282, 2851–2861 (2007). CASPubMed Google Scholar
Tansley, G. H. et al. The cholesterol transporter ABCG1 modulates the subcellular distribution and proteolytic processing of β-amyloid precursor protein. J. Lipid Res.48, 1022–1034 (2007). CASPubMed Google Scholar
Burgess, B. L. et al. ABCG1 influences the brain cholesterol biosynthetic pathway but does not affect amyloid precursor protein or apolipoprotein E metabolism in vivo. J. Lipid Res.49, 1254–1267 (2008). CASPubMed Google Scholar
Perry, V. H. & Holmes, C. Microglial priming in neurodegenerative disease. Nat. Rev. Neurol.10, 217–224 (2014). CASPubMed Google Scholar
Wilcock, D. M. & Griffin, W. S. T. Down's syndrome, neuroinflammation, and Alzheimer neuropathogenesis. J. Neuroinflammation10, 84 (2013). CASPubMedPubMed Central Google Scholar
Griffin, W. S. T. et al. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc. Natl Acad. Sci. USA86, 7611–7615 (1989). CASPubMedPubMed Central Google Scholar
Naude, P. J. W. et al. Serum NGAL is associated with distinct plasma amyloid-β peptides according to the clinical diagnosis of dementia in Down syndrome. J. Alzheimers Dis.45, 733–743 (2015). CASPubMed Google Scholar
Mann, D. M. A. et al. Microglial cells and amyloid-β protein (A) deposition — association with Aβ40-containing plaques. Acta Neuropathol.90, 472–477 (1995). CASPubMed Google Scholar
Xue, Q. S. & Streit, W. J. Microglial pathology in Down syndrome. Acta Neuropathol.122, 455–466 (2011). CASPubMed Google Scholar
Sheng, J. G., Mrak, R. E. & Griffin, W. S. T. S100β protein expression in Alzheimer disease: potential role in the pathogenesis of neuritic plaques. J. Neurosci. Res.39, 398–404 (1994). CASPubMed Google Scholar
Mori, T. et al. Overexpression of human S100B exacerbates cerebral amyloidosis and gliosis in the Tg2576 mouse model of Alzheimer's disease. Glia58, 300–314 (2010). PubMedPubMed Central Google Scholar
Esposito, G. et al. S100B induces tau protein hyperphosphorylation via Dickopff-1 up-regulation and disrupts the Wnt pathway in human neural stem cells. J. Cell. Mol. Med.12, 914–927 (2008). CASPubMedPubMed Central Google Scholar
Chen, C. et al. Role of astroglia in Down's syndrome revealed by patient-derived human-induced pluripotent stem cells. Nat. Commun.5, 4430 (2014). CASPubMed Google Scholar
Mills, S. M. et al. Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial. Rev. Neurol.169, 737–743 (2013). CASPubMed Google Scholar
Bothwell, M. & Giniger, E. Alzheimer's disease: neurodevelopment converges with neurodegeneration. Cell102, 271–273 (2000). CASPubMed Google Scholar
Purro, S. A., Galli, S. & Salinas, P. C. Dysfunction of Wnt signaling and synaptic disassembly in neurodegenerative diseases. J. Mol. Cell Biol.6, 75–80 (2014). CASPubMedPubMed Central Google Scholar
Karmiloff-Smith, A. et al. Genetic and environmental vulnerabilities in children with neurodevelopmental disorders. Proc. Natl Acad. Sci. USA109, 17261–17265 (2012). CASPubMedPubMed Central Google Scholar
Moran, P. M., Higgins, L. S., Cordell, B. & Moser, P. C. Age-related learning-deficits in transgenic mice expressing the 751-amino acid isoform of human β-amyloid precursor protein. Proc. Natl Acad. Sci. USA92, 5341–5345 (1995). CASPubMedPubMed Central Google Scholar
Yamaguchi, F. et al. Transgenic mice for the amyloid precursor protein 695 isoform have impaired spatial memory. Neuroreport2, 781–784 (1991). CASPubMed Google Scholar
Mucke, L. et al. High-level neuronal expression of Aβ1–42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J. Neurosci.20, 4050–4058 (2000). CASPubMedPubMed Central Google Scholar
Balducci, C. & Forloni, G. A.P. P. Transgenic mice: their use and limitations. Neuromolecular Med.13, 117–137 (2011). CASPubMed Google Scholar
Brault, V., Pereira, P., Duchon, A. & Herault, Y. Modeling chromosomes in mouse to explore the function of genes, genomic disorders, and chromosomal organization. PLoS Genet.2, e86 (2006). PubMedPubMed Central Google Scholar
Li, L. B. et al. Trisomy correction in Down syndrome induced pluripotent stem cells. Cell Stem Cell11, 615–619 (2012). CASPubMedPubMed Central Google Scholar
Chang, C. Y. et al. _N_-butylidenephthalide attenuates Alzheimer's disease-like cytopathy in Down syndrome induced pluripotent stem cell-derived neurons. Sci. Rep.5, 8744 (2015). CASPubMedPubMed Central Google Scholar