Early Amyloid Deposition in the Medial Temporal Lobe of Young Down Syndrome Patients: A Regional Quantitative Analysis
Abstract
The presence of the neuropathological alterations of Alzheimer's disease (AD) in essentially all older Down syndrome (DS) patients suggests that the examination of younger DS patients may clarify the early pathological progression of AD. We examined the hippocampus and parahippocampal-inferior temporal gyri of 42 DS patients (ages 4 days to 38 years) for the deposition of amyloid beta protein (Abeta) using both a modified Bielschowsky stain and immunohistochemistry for Abeta protein. The parahippocampal and inferior temporal gyri demonstrated Abeta staining in cases as young as 8 years of age. As age and degree of Abeta deposition increased, staining included the CA-1/subiculum and dentate molecular layer followed then by the remainder of the CA hippocampal regions. The first neuritic plaques were observed in the CA-1/subiculum, despite this being a later region of Abeta deposition. Although Abeta staining increased with age, there was substantial variability in the severity of Abeta deposition within age groups. These results suggest that within the hippocampal/parahippocampal region there is a progressive stereotypic deposition of Abeta. The variable severity of Abeta deposition within age groups suggests that other factors, besides DS, may be contributing to the timing and severity of Abeta deposition.
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Individuals with Down syndrome (T21) are strongly predisposed to Alzheimer's disease, with nearly all exhibiting AD-related neuropathological features by age ∼40 and highly variable onset of dementia thereafter.
“Individuals with Down syndrome (DS), caused by trisomy of chromosome 21 (chr21, T21), are strongly predisposed to Alzheimer’s disease (AD), due to triplication of the APP gene, with ∼100% penetrance of AD brain pathology by age 40 and variable onset of dementia thereafter.”
From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [8]
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
(1968) · Medical Entomology and Zoology · Cited by 4,924 · see citing works
Profound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer’s Disease
Gómez-Isla, T., Price, J. L., McKeel Jr., D. W., Morris, J. C., Growdon, J. H., & Hyman, B. T. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-14-04491.1996 · Cited by 1,796 · see citing works
Paxinos, G., & Jürgen, K. (2004) · Cited by 1,482 · see citing works
Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome
Wisniewski, K. E., Wisniewski, H. M., & Wen, G. Y. (1985) · Annals of Neurology · doi:10.1002/ana.410170310 · Cited by 1,159 · see citing works
Price, J. L., Davis, P. B., Morris, J. C., & White, D. L. (1991) · Neurobiology of Aging · doi:10.1016/0197-4580(91)90006-6 · Cited by 818 · see citing works
Amyloid A4 Protein and Its Precursor in Down's Syndrome and Alzheimer's Disease
Rumble, B. A., Retallack, R. W., Hilbich, C., Simms, G., Multhaup, G., Martins, R. N., Hockey, A., Montgomery, P., Beyreuther, K. T., & Masters, C. L. (1989) · New England Journal of Medicine · doi:10.1056/nejm198906013202203 · Cited by 652 · see citing works
Arriagada, P. V., Marzloff, K., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.9.1681 · Cited by 638 · see citing works
Lemere, C. A., Blusztajn, J. K., Yamaguchi, H., Wisniewski, T., Saido, T. C., & Selkoe, D. J. (1996) · Neurobiology of Disease · doi:10.1006/nbdi.1996.0003 · Cited by 584 · see citing works
Amyloid β-protein deposition in tissues other than brain in Alzheimer's disease
Joachim, C. L., Mori, H., & Selkoe, D. J. (1989) · Nature · doi:10.1038/341226a0 · Cited by 462 · see citing works
The pathological association between down syndrome and Alzheimer disease
Mann, D. M. A. (1988) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(88)90041-3 · Cited by 346 · see citing works
Burger, P. C., & Vogel, F. S. (1973) · PubMed · Cited by 342 · see citing works
Presence of soluble amyloid β–peptide precedes amyloid plaque formation in Down's syndrome
Teller, J. K., Russo, C., DeBusk, L. M., Angelini, G., Zaccheo, D., Dagna-Bricarelli, F., Scartezzini, P., Bertolini, S., Mann, D. M. A., Tabaton, M., et al. (1996) · Nature Medicine · doi:10.1038/nm0196-93 · Cited by 328 · see citing works
Hyman, B., Marzloff, K., & Arriagada, P. (1993) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199311000-00006 · Cited by 294 · see citing works
PRESENILE DEMENTIA AND ALZHEIMER'S DISEASE IN MONGOLISM
Olson, M. I., & Shaw, C. (1969) · Brain · doi:10.1093/brain/92.1.147 · Cited by 290 · see citing works
Bouras, C., Hof, P. R., Giannakopoulos, P., Michel, J.-P., & Morrison, J. H. (1994) · Cerebral Cortex · doi:10.1093/cercor/4.2.138 · Cited by 280 · see citing works
Hof, P., Bouras, C., Perl, D. P., Sparks, D., Mehta, N. A., & Morrison, J. H. (1995) · Archives of Neurology · doi:10.1001/archneur.1995.00540280065020 · Cited by 237 · see citing works
Down patients: Extracellular preamyloid deposits precede neuritic degeneration and senile plaques
Giaccone, G., Tagliavini, F., Linoli, G., Bouras, C., Frigerio, L., Frangione, B., & Bugiani, O. (1989) · Neuroscience Letters · doi:10.1016/0304-3940(89)90169-9 · Cited by 231 · see citing works
EARLY SENILE DEMENTIA IN MONGOLOID IDIOCY
Jervis, G. A. (1948) · American Journal of Psychiatry · doi:10.1176/ajp.105.2.102 · Cited by 227 · see citing works
Mental Retardation: A Review of Research
Roland, C. G. (1965) · JAMA · doi:10.1001/jama.1965.03080040092048 · Cited by 180 · see citing works
Neuropathological Changes in Down's Syndrome Hippocampal Formation
Hyman, B. T. (1995) · Archives of Neurology · doi:10.1001/archneur.1995.00540280059019 · Cited by 149 · see citing works
Hyman, B. T., Tanzi, R. E., Marzloff, K., Barbour, R., & Schenk, D. (1992) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199201000-00009 · Cited by 135 · see citing works
Comparison of four staining methods on the detection of neuritic plaques
Wı́sniewski, H. M., Wen, G. Y., & Kim, K. S. (1989) · Acta Neuropathologica · doi:10.1007/bf00687398 · Cited by 124 · see citing works
Royston, M. C., Mann, D. M. A., Pickering-Brown, S. M., Owen, F., Perry, R., Raghavan, R., Khin-IMu, C., Tyrer, S. P., Day, K. A., Crook, R., et al. (1994) · Neuroreport · doi:10.1097/00001756-199412000-00044 · Cited by 94 · see citing works
The Site of the Earliest Lesions of Alzheimer's Disease
Mann, D. M., & Esiri, M. M. (1988) · New England Journal of Medicine · doi:10.1056/nejm198803243181218 · Cited by 94 · see citing works
Láng, E., Szendrei, G. I., Lee, V. M. ‐., & Ötvös, L. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)91264-q · Cited by 86 · see citing works
Histopathologische Untersuchungen über Entstehung und Wesen der senilen Plaques
Struwe, F. E. (1929) · Zeitschrift für die gesamte Neurologie und Psychiatrie · doi:10.1007/bf02876635 · Cited by 79 · see citing works
Mann, D. M. A., BROWN, A., Prinja, D., Davies, C. A., Landon, M., Masters, C. L., & Beyreuther, K. (1989) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1989.tb01232.x · Cited by 74 · see citing works
Mann, D. M. A., BROWN, A. M. T., Prinja, D., JONES, D., & Davies, C. A. (1990) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1990.tb00928.x · Cited by 69 · see citing works
Stevens, H. A., & Heber, R. F. (1965) · The American Journal of the Medical Sciences · doi:10.1097/00000441-196505000-00037 · Cited by 67 · see citing works
Murphy, G. M., Eng, L. F., Ellis, W. G., Perry, G. L., Meissner, L. C., & Tinklenberg, J. R. (1990) · Brain Research · doi:10.1016/0006-8993(90)90345-c · Cited by 46 · see citing works
Raghavan, R., Khin-Nu, C., Brown, A. G., Day, K. A., Tyrer, S. P., Ince, P. G., Perry, E. K., & Perry, R. H. (1994) · Neuroreport · doi:10.1097/00001756-199406000-00026 · Cited by 31 · see citing works
Flagged first, then by citations
1 of the 33 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Phases of Aβ-deposition in the human brain and its relevance for the development of AD
Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002) · Neurology · doi:10.1212/wnl.58.12.1791 · Cited by 3,490 · see citing works
Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years
Braak, H., Thal, D. R., Ghebremedhin, E., & Del Tredici, K. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318232a379 · Cited by 2,194 · see citing works
A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome
Wiseman, F. K., Al-Janabi, T., Hardy, J., Karmiloff-Smith, A., Nizetic, D., Tybulewicz, V. L. J., Fisher, E. M. C., & Strydom, A. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3983 · Cited by 562 · see citing works
Cognitive deficits and associated neurological complications in individuals with Down's syndrome
Lott, I. T., & Dierssen, M. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70112-5 · Cited by 484 · see citing works
Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy
Zheng, Q., & Wang, X. (2024) · Protein & Cell · doi:10.1093/procel/pwae026 · Cited by 454 · see citing works
D'Andrea, M. R., Nagele, R. G., Wang, H., Peterson, P. A., & Lee, D. H. S. (2001) · Histopathology · doi:10.1046/j.1365-2559.2001.01082.x · Cited by 390 · see citing works
Dementia in Down syndrome: unique insights for Alzheimer disease research
Lott, I. T., & Head, E. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0132-6 · Cited by 383 · see citing works
Sequence of Aβ-protein deposition in the human medial temporal lobe
Thal, D. R., Rüb, U., Schultz, C., Sassin, I., Ghebremedhin, E., Del Tredici, K., Braak, E., & Braak, H. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.8.733 · Cited by 370 · see citing works
Alzheimer's disease associated with Down syndrome: a genetic form of dementia
Fortea, J., Zaman, S. H., Hartley, S., Rafii, M. S., Head, E., & Carmona-Iragui, M. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00245-3 · Cited by 357 · see citing works
Aging in Down Syndrome and the Development of Alzheimer's Disease Neuropathology
Head, E., T. Lott, I., M. Wilcock, D., & A. Lemere, C. (2015) · Current Alzheimer Research · doi:10.2174/1567205012666151020114607 · Cited by 289 · see citing works
Marzia Perluigi, A., Domenico, F. D., & Butterfield, D. A. (2023) · Physiological Reviews · doi:10.1152/physrev.00030.2022 · Cited by 306 · see citing works
Brain, aging and neurodegeneration: Role of zinc ion availability
Mocchegiani, E., Bertoni–Freddari, C., Marcellini, F., & Malavolta, M. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.04.005 · Cited by 280 · see citing works
Alzheimer's disease in Down syndrome: Neurobiology and risk
Zigman, W. B., & Lott, I. T. (2007) · Mental Retardation and Developmental Disabilities Research Reviews · doi:10.1002/mrdd.20163 · Cited by 279 · see citing works
Human astrocytes in the diseased brain
Dossi, E., Vasile, F., & Rouach, N. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2017.02.001 · Cited by 250 · see citing works
Time Course of the Development of Alzheimer-like Pathology in the Doubly Transgenic PS1+APP Mouse
Gordon, M. N., Holcomb, L. A., Jantzen, P. T., DiCarlo, G., Wilcock, D., Boyett, K. W., Connor, K., Melachrino, J., O'Callaghan, J. P., & Morgan, D. (2002) · Experimental Neurology · doi:10.1006/exnr.2001.7754 · Cited by 247 · see citing works
The genetics and neuropathology of Alzheimer’s disease
Schellenberg, G. D., & Montine, T. J. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-0996-2 · Cited by 242 · see citing works
The Development of Amyloid β Protein Deposits in the Aged Brain
Thal, D. R., Capetillo-Zarate, E., Del Tredici, K., & Braak, H. (2006) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2006.6.re1 · Cited by 234 · see citing works
Neuropathology of Alzheimer’s disease: a critical update
Jellinger, K. A., & Bancher, C. (1998) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-7508-8_8 · Cited by 231 · see citing works
Down’s syndrome, neuroinflammation, and Alzheimer neuropathogenesis
Wilcock, D. M., & Griffin, W. S. T. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-84 · Cited by 230 · see citing works
Neurological phenotypes for Down syndrome across the life span
Lott, I. T. (2012) · Progress in Brain Research · doi:10.1016/b978-0-444-54299-1.00006-6 · Cited by 225 · see citing works
Alzheimer disease and Down syndrome: factors in pathogenesis
Lott, I. T., & Head, E. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.08.005 · Cited by 212 · see citing works
The importance of understanding individual differences in Down syndrome
Karmiloff‐Smith, A., Al‐Janabi, T., D’Souza, H., Groet, J., Massand, E., Mok, K. Y., Startin, C. M., Fisher, E., Hardy, J., Nižetić, D., et al. (2016) · F1000Research · doi:10.12688/f1000research.7506.1 · Cited by 210 · see citing works
Ferrer, I. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.03.005 · Cited by 174 · see citing works
Costa, A. C. S., Scott-McKean, J. J., & Stasko, M. R. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301535 · Cited by 163 · see citing works
Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain
Perluigi, M., Pupo, G., Tramutola, A., Cini, C., Coccia, R., Barone, E., Head, E., Butterfield, D. A., & Di Domenico, F. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.04.007 · Cited by 155 · see citing works
Colacurcio, D. J., Pensalfini, A., Jiang, Y., & Nixon, R. A. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.10.001 · Cited by 167 · see citing works
Down syndrome and Alzheimer's disease: A link between development and aging
Lott, I. T., & Head, E. (2001) · Mental Retardation and Developmental Disabilities Research Reviews · doi:10.1002/mrdd.1025 · Cited by 157 · see citing works
Davidson, Y. S., Robinson, A., Prasher, V. P., & Mann, D. M. A. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0559-4 · Cited by 141 · see citing works
Wiseman, F. K., Pulford, L. J., Barkus, C., Liao, F., Portelius, E., Webb, R., Chávez-Gutiérrez, L., Cleverley, K., Noy, S., Sheppard, O., et al. (2018) · Brain · doi:10.1093/brain/awy159 · Cited by 133 · see citing works
Alzheimer's Disease Amyloid-β Links Lens and Brain Pathology in Down Syndrome
Moncaster, J. A., Pineda, R., Moir, R. D., Lu, S., Burton, M. A., Ghosh, J. G., Ericsson, M., Soscia, S. J., Mocofanescu, A., Folkerth, R. D., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010659 · Cited by 142 · see citing works
The GABAergic Hypothesis for Cognitive Disabilities in Down Syndrome
Contestabile, A., Magara, S., & Cancedda, L. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00054 · Cited by 141 · see citing works
Oxidative stress: A bridge between Down's syndrome and Alzheimer's disease
Zana, M., Janka, Z., & Kalman, J. L. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.03.008 · Cited by 137 · see citing works
Alzheimer's Disease in Down Syndrome.
Head, E., Powell, D. K., Gold, B. T., & Schmitt, F. A. (2012) · PubMed · Cited by 139 · see citing works
Nerve growth factor metabolic dysfunction in Alzheimer's disease and Down syndrome
Iulita, M. F., & Cuello, A. C. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.04.010 · Cited by 135 · see citing works
Nistor, M., Don, M., Parekh, M., Sarsoza, F. M., Goodus, M. T., López, G., Kawas, C. H., Leverenz, J. B., Doran, E. W., Lott, I. T., et al. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.06.023 · Cited by 135 · see citing works
Self-citationCommunication breaks-Down: From neurodevelopment defects to cognitive disabilities in Down syndrome
Contestabile, A., Benfenati, F., & Gasparini, L. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.01.003 · Cited by 134 · see citing works
Domenico, F. D., Coccia, R., Cocciolo, A., Murphy, M. P., Cenini, G., Head, E., Butterfield, D. A., Giorgi, A., Schininà, M. E., Mancuso, C., et al. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.04.013 · Cited by 133 · see citing works
Secretase Targets for Alzheimer's Disease: Identification and Therapeutic Potential
Wolfe, M. S. (2001) · Journal of Medicinal Chemistry · doi:10.1021/jm0004897 · Cited by 133 · see citing works
FAD mutant PS-1 gene-targeted mice: increased Aβ42 and Aβ deposition without APP overproduction
Flood, D. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00330-x · Cited by 131 · see citing works
Payne, C., Machado, C. J., Bliwise, N. G., & Bachevalier, J. (2010) · Hippocampus · doi:10.1002/hipo.20688 · Cited by 129 · see citing works
Cenini, G., Dowling, A. L. S., Beckett, T. L., Barone, E., Mancuso, C., Murphy, M. P., LeVine, H., Lott, I. T., Schmitt, F. A., Butterfield, D. A., et al. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.10.001 · Cited by 122 · see citing works
Węgiel, J., Dowjat, K., Kaczmarski, W., Kuchna, I., Nowicki, K., Frackowiak, J., Mazur‐Kolecka, B., Wegiel, J., Silverman, W. P., Reisberg, ., et al. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0419-6 · Cited by 113 · see citing works
Wilcock, D. M., Hurban, J., Helman, A. M., Sudduth, T. L., McCarty, K. L., Beckett, T. L., Ferrell, J. C., Murphy, M. P., Abner, E. L., Schmitt, F. A., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.05.016 · Cited by 110 · see citing works
Down Syndrome: Advances in Molecular Biology and the Neurosciences
Capone, G. T. (2001) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/00004703-200102000-00007 · Cited by 110 · see citing works
Chiarini, A., Armato, U., Gardenal, E., Gui, L., & Prà, I. D. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00217 · Cited by 105 · see citing works
Neuroinflammation in the Aging Down Syndrome Brain; Lessons from Alzheimer's Disease
Wilcock, D. M. (2012) · Current Gerontology and Geriatrics Research · doi:10.1155/2012/170276 · Cited by 104 · see citing works
Estrogen restores cognition and cholinergic phenotype in an animal model of Down syndrome
Granholm, A., Ford, K. A., Hyde, L. A., Bimonte, H. A., Hunter, C. L., NELSON, M., Albeck, D. S., Sanders, L., Mufson, E. J., & Crnic, L. S. (2002) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00884-3 · Cited by 104 · see citing works
Spatial Vision Deficits in Infants and Children with Down Syndrome
John, F. M. (2004) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.03-0951 · Cited by 104 · see citing works
Head, E., Azizeh, B. Y., Lott, I. T., Tenner, A. J., Cotman, C. W., & Cribbs, D. H. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0380 · Cited by 103 · see citing works
Chapter 4 Alzheimer's Disease in Adults with Down Syndrome
Zigman, W. B., Devenny, D. A., Krinsky‐McHale, S. J., Jenkins, E. C., Urv, T. K., Węgiel, J., Schupf, N., & Silverman, W. P. (2008) · International review of research in mental retardation · doi:10.1016/s0074-7750(08)00004-9 · Cited by 99 · see citing works
García-Cerro, S., Rueda, N., Vidal, V., Lantigua, S., & Martínez-Cué, C. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.06.010 · Cited by 100 · see citing works
The impact of sleep disruption on executive function in Down syndrome
Chen, C., Spanò, G., & Edgin, J. O. (2013) · Research in Developmental Disabilities · doi:10.1016/j.ridd.2013.03.009 · Cited by 98 · see citing works
Węgiel, J., Kaczmarski, W., Barua, M., Kuchna, I., Nowicki, K., Wang, K.-C., Wegiel, J., Mazur‐Kolecka, B., Frackowiak, J., Mazur‐Kolecka, B., et al. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318202bfa1 · Cited by 98 · see citing works
Domenico, F. D., Pupo, G., Tramutola, A., Giorgi, A., Schininà, M. E., Coccia, R., Head, E., Butterfield, D. A., & Marzia Perluigi, A. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.03.027 · Cited by 98 · see citing works
Kulstad, J. J., McMillan, P. J., Leverenz, J. B., Cook, D. G., Green, P. S., Peskind, E. R., Wilkinson, C. W., Farris, W., Mehta, P. D., & Craft, S. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.2.139 · Cited by 96 · see citing works
Self-citationLiu, K., Solano, I., Mann, D. M. A., Lemere, C. A., Mercken, M. H., Trojanowski, J. Q., & Lee, V. M. ‐. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0077-5 · Cited by 94 · see citing works
Postnatal Development of the Primate Hippocampal Formation
Lavenex, P., Lavenex, P. B., & Amaral, D. G. (2006) · Developmental Neuroscience · doi:10.1159/000096222 · Cited by 92 · see citing works
Head, E., Lott, I. T., Patterson, D. W., Doran, E. W., & Haier, R. J. (2007) · Journal of Alzheimer s Disease · doi:10.3233/jad-2007-11110 · Cited by 89 · see citing works
Anderson, A. J., Stoltzner, S., Lai, F., Su, J. H., & Nixon, R. A. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00126-3 · Cited by 87 · see citing works
Zheng, Q., Li, G., Wang, S., Zhou, Y., Liu, K., Gao, Y., Zhou, Y., Zheng, L., Zhu, L., Deng, Q., et al. (2021) · Science Advances · doi:10.1126/sciadv.abe1340 · Cited by 85 · see citing works
Cognition in Down syndrome: a developmental cognitive neuroscience perspective
Edgin, J. O. (2013) · Wiley Interdisciplinary Reviews Cognitive Science · doi:10.1002/wcs.1221 · Cited by 82 · see citing works
Galdzicki, Z., Siarey, R. J., Pearce, R., Stoll, J., & Rapoport, S. I. (2001) · Brain Research Reviews · doi:10.1016/s0926-6410(00)00074-4 · Cited by 81 · see citing works
Prospects for Improving Brain Function in Individuals with Down Syndrome
Costa, A. C. S., & Scott-McKean, J. J. (2013) · CNS Drugs · doi:10.1007/s40263-013-0089-3 · Cited by 81 · see citing works
Amyloid-β and Astrocytes Interplay in Amyloid-β Related Disorders
Batarseh, Y. S., Duong, Q.-V., Mousa, Y. M., Rihani, S. B. A., Elfakhri, K. H., & Kaddoumi, A. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17030338 · Cited by 82 · see citing works
Single cell gene expression profiling in Alzheimer’s disease
Ginsberg, S. D., Che, S., Counts, S., & Mufson, E. J. (2006) · NeuroRx · doi:10.1016/j.nurx.2006.05.007 · Cited by 76 · see citing works
Di Domenico, F., Pupo, G., Mancuso, C., Barone, E., Paolini, F., Arena, A., Blarzino, C., Schmitt, F. A., Head, E., Butterfield, D. A., et al. (2015) · Journal of Alzheimer’s Disease · doi:10.3233/jad-141254 · Cited by 75 · see citing works
β2-microglobulin functions as an endogenous NMDAR antagonist to impair synaptic function
Gao, Y., Hong, Y., Huang, L., Zheng, S., Zhang, H., Wang, S., Yao, Y., Zhao, Y., Zhu, L., Xu, Q., et al. (2023) · Cell · doi:10.1016/j.cell.2023.01.021 · Cited by 75 · see citing works
Prà, I. D., Chiarini, A., Gui, L., Chakravarthy, B., Pacchiana, R., Gardenal, E., Whitfield, J. F., & Armato, U. (2014) · The Neuroscientist · doi:10.1177/1073858414529828 · Cited by 73 · see citing works
Strupp, B. J., Powers, B. E., Velázquez, R., Ash, J. A., Kelley, C. M., Alldred, M. J., Strawderman, M. S., Caudill, M. A., Mufson, E. J., & Ginsberg, S. D. (2015) · Current Alzheimer Research · doi:10.2174/1567205012666150921100311 · Cited by 71 · see citing works
Zheng, Q., Song, B., Li, G., Cai, F., Wu, M., Zhao, Y., Jiang, L., Guo, T., Shen, M., Hou, H., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci152170 · Cited by 73 · see citing works
Age dependence of brain β-amyloid deposition in Down syndrome
Jennings, D. L., Seibyl, J. P., Sabbagh, M. N., Lai, F., Hopkins, W. E., Bullich, S., Gimenez, M., Reininger, C. B., Pütz, B., Stephens, A. W., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001212 · Cited by 74 · see citing works
Positron Emission Tomography of Brain β-Amyloid and Tau Levels in Adults With Down Syndrome
Nelson, L. D., Siddarth, P., Kepe, V., Scheibel, K. E., Huang, S. C., Barrio, J. R., & Small, G. W. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.104 · Cited by 72 · see citing works
Aging with Down Syndrome—Where Are We Now and Where Are We Going?
Alldred, M. J., Martini, A. C., Patterson, D., Hendrix, J. A., & Granholm, A. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10204687 · Cited by 70 · see citing works
Shen, Q., Loewenstein, D., Potter, E., Zhao, W., Appel, J., Greig, M. T., Raj, A., Acevedo, A., Schofield, E., Barker, W., et al. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.07.002 · Cited by 68 · see citing works
The NGF Metabolic Pathway in the CNS and its Dysregulation in Down Syndrome and Alzheimer's Disease
Iulita, M. F., & Cuello, A. C. (2015) · Current Alzheimer Research · doi:10.2174/1567205012666150921100030 · Cited by 67 · see citing works
Zinc-bound metallothioneins as potential biological markers of ageing
Mocchegiani, E., Giacconi, R., Cipriano, C., Muzzioli, M., Fattoretti, P., Bertoni–Freddari, C., Isani, G., Zambenedetti, P., & Zatta, P. F. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00468-3 · Cited by 64 · see citing works
Kaur, G., Sharma, A., Xu, W., Gerum, S., Alldred, M. J., Subbanna, S., Basavarajappa, B. S., Pawlik, M., Ohno, M., Ginsberg, S. D., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.5338-13.2014 · Cited by 58 · see citing works
Alzheimer's disease therapeutic research: the path forward
Aisen, P. S. S. (2009) · Alzheimer s Research & Therapy · doi:10.1186/alzrt2 · Cited by 57 · see citing works
Cerebrovascular contributions to aging and Alzheimer's disease in Down syndrome
Wilcock, D. M., Schmitt, F. A., & Head, E. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.11.007 · Cited by 56 · see citing works
Cognitive Functioning in Children with Down Syndrome: Current Knowledge and Future Directions
Lukowski, A. F., Milojevich, H. M., & Eales, L. (2019) · Advances in child development and behavior · doi:10.1016/bs.acdb.2019.01.002 · Cited by 56 · see citing works
Neurogenetic disorders across the lifespan: from aberrant development to degeneration
Hickman, R. A., O’Shea, S. A., Mehler, M. F., & Chung, W. K. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-021-00595-5 · Cited by 53 · see citing works
Exploring Alzheimer Molecular Pathology in Down's Syndrome Cerebrospinal Fluid
Portelius, E., Soininen, H. S., Andréasson, U., Zetterberg, H., Persson, R., Karlsson, G., Blennow, K., Herukka, S., & Mattsson, N. (2014) · Neurodegenerative Diseases · doi:10.1159/000358800 · Cited by 50 · see citing works
Sabbagh, M. N. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.535 · Cited by 52 · see citing works
Poor Sleep as a Precursor to Cognitive Decline in Down Syndrome : A Hypothesis
Fernandez, F. (2013) · Journal of Alzheimer’s Disease & Parkinsonism · doi:10.4172/2161-0460.1000124 · Cited by 49 · see citing works
Perez, S. E., Miguel, J. C., He, B., Malek‐Ahmadi, M. H., Abrahamson, E. E., Ikonomović, M. D., Lott, I. T., Doran, E. W., Alldred, M. J., Ginsberg, S. D., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-01965-6 · Cited by 47 · see citing works
Rafii, M. S., Kleschevnikov, A. M., Sawa, M., & Mobley, W. C. (2019) · Handbook of clinical neurology · doi:10.1016/b978-0-12-804766-8.00017-0 · Cited by 52 · see citing works
Granholm, A., Sanders, L., Seo, H., Lin, L., Ford, K. A., & Ole Isacson, A. (2003) · Hippocampus · doi:10.1002/hipo.10130 · Cited by 49 · see citing works
BACE-2 is overexpressed in Down’s syndrome
Barbiero, L., Benussi, L., Ghidoni, R., Alberici, A., Russo, C., Schettini, G., Pagano, S., Parati, E. A., Mazzoli, F., Nicosia, F. M., et al. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00049-9 · Cited by 49 · see citing works
Colombo, J. A., Reisin, H. D., Jones, M., & Bentham, C. (2005) · Experimental Neurology · doi:10.1016/j.expneurol.2004.11.024 · Cited by 48 · see citing works
Ringenbach, S. D. R., Holzapfel, S. D., Mulvey, G. M., Jimenez, A., Benson, A. M., & Richter, M. (2016) · Journal of Intellectual Disability Research · doi:10.1111/jir.12275 · Cited by 48 · see citing works
Down syndrome, beta-amyloid and neuroimaging
Head, E., Helman, A. M., Powell, D. K., & Schmitt, F. A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.09.013 · Cited by 45 · see citing works
Age-dependent oxidative stress-induced DNA damage in Down’s lymphocytes
Zana, M., Szécsényi, A., Czibula, Á., Bjelik, A., Juhász, A., Rimanóczy, Á., Szabó, K., Vetró, Á., Szűcs, P., Várkonyi, Á., et al. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.04.167 · Cited by 45 · see citing works
Neuropathological correlates of amyloid PET imaging in Down syndrome
Abrahamson, E. E., Head, E., Lott, I. T., Handen, B. L., Mufson, E. J., Christian, B. T., Klunk, W. E., & Ikonomović, M. D. (2019) · Developmental Neurobiology · doi:10.1002/dneu.22713 · Cited by 45 · see citing works
Sarsoza, F. M., Saing, T., Kayed, R., Dahlin, R., Dick, M. B., Broadwater-Hollifield, C., Mobley, S., Lott, I. T., Doran, E. W., Gillen, D. L., et al. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0530-3 · Cited by 44 · see citing works
Alzheimer's Disease and Down Syndrome: From Meiosis to Dementia
Petronis, A. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7128 · Cited by 44 · see citing works
Costa, A. C. S. (2011) · Developmental Neuroscience · doi:10.1159/000330861 · Cited by 44 · see citing works
Dekker, A. D., Coppus, A. M. W., Vermeiren, Y., Aerts, T., van Duijn, C. M., Kremer, B. P. H., Naudé, P., Dam, D. V., & Deyn, P. P. D. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140783 · Cited by 42 · see citing works
Dissecting Alzheimer disease in Down syndrome using mouse models
Choong, X. Y., Tosh, J., Pulford, L. J., & Fisher, E. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00268 · Cited by 40 · see citing works
Pentz, R., Iulita, M. F., Ducatenzeiler, A., Videla, L., Benejam, B., Carmona‐Iragui, M., Blesa, R., Lleó, A., Fortea, J., & Cuello, A. C. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12229 · Cited by 40 · see citing works
Maxwell, A. M., Yuan, P., Rivera, B. M., Schaaf, W., Mladinov, M., Prasher, V. P., Robinson, A. C., DeGrado, W. F., & Condello, C. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01298-0 · Cited by 23 · see citing works
- Authors
- Leverenz, J. B., & Raskind, M. A.
- Affiliations
- University of Washington (US)
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 1998-04
- Volume
- 150
- Issue
- 2
- Pages
- 296-304
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W1994573232
- Cited by
- 214
- References
- 33
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 10 · 2023: 10 · 2022: 9 · 2021: 14 · 2020: 9 · 2019: 11 · 2018: 7 · 2017: 12 · 2016: 4 · 2015: 15 · 2014: 17 · 2013: 7 · 2012: 9
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AGE-WELL
- Ministerul Cercetării, Inovării şi Digitalizării
- National Institute on Aging (AG 05136, AG00503, P50AG005136)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Down syndrome, amyloid-beta deposition, Alzheimer's disease, medial temporal lobe, hippocampus, parahippocampal gyrus, inferior temporal gyrus, neuritic plaques
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aging, Alzheimer Disease, Child, Child, Preschool, Down Syndrome, Female, Hippocampus, Humans, Immunohistochemistry, Infant, Infant, Newborn, Male, Organ Specificity, Reference Values, Regression Analysis, Temporal Lobe, Amyloid beta-Peptides
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