Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain
Open accessPublished version of a preprint
Abstract
A population of more than six million people worldwide at high risk of Alzheimer’s disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of β-amyloid-(Aβ)-precursor-protein gene. We report AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The pathology consisted of extracellular diffuse and fibrillar Aβ deposits, hyperphosphorylated/pathologically conformed Tau, and premature neuronal loss. Presence/absence of AD-like pathology was donor-specific (reproducible between individual organoids/iPSC lines/experiments). Pathology could be triggered in pathology-negative T21 organoids by CRISPR/Cas9-mediated elimination of the third copy of chromosome 21 gene BACE2 , but prevented by combined chemical β and γ-secretase inhibition. We found that T21 organoids secrete increased proportions of Aβ-preventing (Aβ1–19) and Aβ-degradation products (Aβ1–20 and Aβ1–34). We show these profiles mirror in cerebrospinal fluid of people with DS. We demonstrate that this protective mechanism is mediated by BACE2 -trisomy and cross-inhibited by clinically trialled BACE1 inhibitors. Combined, our data prove the physiological role of BACE2 as a dose-sensitive AD-suppressor gene, potentially explaining the dementia delay in ~30% of people with DS. We also show that DS cerebral organoids could be explored as pre-morbid AD-risk population detector and a system for hypothesis-free drug screens as well as identification of natural suppressor genes for neurodegenerative diseases.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Evidence in preclinical models demonstrates that genes other than APP being in three copies modify aspects of DSAD, such as cognition and amyloid-β load.
“Evidence in preclinical models demonstrates that genes other than APP being in three copies modify aspects of DSAD, such as cognition and amyloid-β load [1, 50, 70]”
From Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome–Alzheimer’s disease (2025) · cites this paper as [1]
The Results section (‘Trisomy of BACE2 skews non-amyloidogenic Aβ peptide ratios and suppresses AD-like pathology in organoids’; page unavailable) reports that removing the third BACE2 copy led to amyloid deposits in trisomy 21 cerebral organoids. This supports the claim about a gene other than APP modifying amyloid pathology in a preclinical model, but the paper does not demonstrate an effect on cognition. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Self-citationAmyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Amyloid plaque core protein in Alzheimer disease and Down syndrome.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4245 · Cited by 4,431 · see citing works
Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., et al. (1999) · Science · doi:10.1126/science.286.5440.735 · Cited by 3,876 · cited 1× · see citing works
“BACE1 is the main β -secretase in the brain [9], whereas the expression and function of its homologue BACE2 (encoded by a chromosome 21 gene) remain less clear [10, 11].”
Scheltens, P., Blennow, K., Breteler, M. M. B., de Strooper, B., Frisoni, G. B., Salloway, S., & Van der Flier, W. M. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01124-1 · Cited by 3,125 · see citing works
Self-citationHigh-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects
Kleinstiver, B. P., Pattanayak, V., Prew, M. S., Tsai, S. Q., Nguyen, N. T., Zheng, Z., & Joung, J. K. (2016) · Nature · doi:10.1038/nature16526 · Cited by 2,673 · see citing works
Decreased Clearance of CNS β-Amyloid in Alzheimer’s Disease
Mawuenyega, K. G., Sigurdson, W., Ovod, V., Munsell, L., Kasten, T., Morris, J. C., Yarasheski, K. E., & Bateman, R. J. (2010) · Science · doi:10.1126/science.1197623 · Cited by 2,078 · see citing works
Generation of cerebral organoids from human pluripotent stem cells
Lancaster, M. A., & Knoblich, J. A. (2014) · Nature Protocols · doi:10.1038/nprot.2014.158 · Cited by 1,766 · see citing works
The coming of age of chaperone-mediated autophagy
Kaushik, S., & Cuervo, A. M. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0001-6 · Cited by 1,422 · see citing works
Rovelet‐Lecrux, A., Hannequin, D., Raux, G., Meur, N. L., Laquerrière, A., Vital, A., Dumanchin‐Njock, C., Feuillette, S., Brice, A., Vercelletto, M., et al. (2005) · Nature Genetics · doi:10.1038/ng1718 · Cited by 1,249 · see citing works
Self-citationGoedert, M., Spillantini, M. G., Cairns, N. J., & Crowther, R. A. (1992) · Neuron · doi:10.1016/0896-6273(92)90117-v · Cited by 1,114 · see citing works
CCTop: An intuitive, flexible and reliable CRISPR/Cas9 target prediction tool
Stemmer, M., Thumberger, T., del Sol Keyer, M., Wittbrodt, J., & Mateo, J. L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0124633 · Cited by 1,088 · see citing works
Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease
Yu, W. H., Cuervo, A. M., Kumar, A., Peterhoff, C. M., Schmidt, S. D., Lee, J.-H., Mohan, P. S., Mercken, M., Farmery, M. R., Tjernberg, L. O., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200505082 · Cited by 967 · see citing works
The secretases: enzymes with therapeutic potential in Alzheimer disease
De Strooper, B., Vassar, R., & Golde, T. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.218 · Cited by 799 · 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
Self-citationSalehi, A., Delcroix, J.-D., Belichenko, P. V., Zhan, K., Wu, C., Valletta, J. S., Takimoto-Kimura, R., Kleschevnikov, A. M., Sambamurti, K., Chung, P. P., et al. (2006) · Neuron · doi:10.1016/j.neuron.2006.05.022 · Cited by 543 · see citing works
Modeling amyloid beta and tau pathology in human cerebral organoids
Gonzalez, C., Armijo, E., Bravo-Alegria, J., Becerra-Calixto, A., Mays, C. E., & Soto, C. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0229-8 · Cited by 430 · see citing works
η-Secretase processing of APP inhibits neuronal activity in the hippocampus
Willem, M., Tahirovic, S., Busche, M. A., Ovsepian, S. V., Chafai, M., Kootar, S., Hornburg, D., Evans, L. D. B., Moore, S., Daria, A., et al. (2015) · Nature · doi:10.1038/nature14864 · Cited by 398 · see citing works
BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease
Vassar, R. (2014) · Alzheimer's Research & Therapy · doi:10.1186/s13195-014-0089-7 · Cited by 393 · see citing works
Proteolytic Degradation of Amyloid -Protein
Saido, T., & Leissring, M. A. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006379 · Cited by 368 · see citing works
Phenotypic and Biochemical Analyses of BACE1- and BACE2-deficient Mice
Dominguez, D. I., Tournoy, J., Hartmann, D., Huth, T., Cryns, K., Deforce, S., Serneels, L., Espuny-Camacho, I., Marjaux, E., Craessaerts, K., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505249200 · Cited by 359 · see citing works
Vassar, R. J., Kuhn, P., Haass, C., Kennedy, M. E., Rajendran, L., Wong, P. C., & Lichtenthaler, S. F. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12715 · Cited by 329 · 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 326 · see citing works
Expression Analysis of BACE2 in Brain and Peripheral Tissues
Bennett, B. D., Babu-Khan, S., Loeloff, R., Louis, J.-C., Curran, E., Citron, M., & Vassar, R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002688200 · Cited by 317 · see citing works
Unique properties of lamp2a compared to other lamp2 isoforms
Cuervo, A. M., & Dice, J. F. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.24.4441 · Cited by 304 · see citing works
Hallmarks of Alzheimer’s Disease in Stem-Cell-Derived Human Neurons Transplanted into Mouse Brain
Espuny-Camacho, I., Arranz, A. M., Fiers, M., Snellinx, A., Ando, K., Munck, S., Bonnefont, J., Lambot, L., Corthout, N., Omodho, L., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.02.001 · Cited by 244 · see citing works
Self-citationSomatic APP gene recombination in Alzheimer’s disease and normal neurons
Lee, M.-H., Siddoway, B., Kaeser, G. E., Segota, I., Rivera, R., Romanow, W. J., Liu, C. S., Park, C., Kennedy, G., Long, T., et al. (2018) · Nature · doi:10.1038/s41586-018-0718-6 · Cited by 210 · see citing works
The BACE‐1 inhibitor CNP520 for prevention trials in Alzheimer's disease
Neumann, U., Ufer, M., Jacobson, L. H., Rouzade‐Dominguez, M., Huledal, G., Kolly, C., Lüönd, R. M., Machauer, R., Veenstra, S. J., Hurth, K., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201809316 · Cited by 177 · see citing works
Association of Dementia With Mortality Among Adults With Down Syndrome Older Than 35 Years
Hithersay, R., Startin, C. M., Hamburg, S., Mok, K. Y., Hardy, J., Fisher, E. M. C., Tybulewicz, V. L. J., Nizetic, D., & Strydom, A. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2018.3616 · Cited by 176 · see citing works
Self-citationSun, X., He, G., & Song, W. (2006) · The FASEB Journal · doi:10.1096/fj.05-5632com · Cited by 156 · see citing works
Portelius, E., Tran, A. J., Andréasson, U., Persson, R., Brinkmalm, G., Zetterberg, H., Blennow, K., & Brinkmalm, A. (2007) · Journal of Proteome Research · doi:10.1021/pr0703627 · Cited by 146 · see citing works
Self-citationWiseman, 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
Self-citationBACE1 and BACE2 enzymatic activities in Alzheimer’s disease
Ahmed, R. R., Holler, C. J., Webb, R. L., Li, F., Beckett, T. L., & Murphy, M. P. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06528.x · Cited by 127 · see citing works
A non‐amyloidogenic function of BACE‐2 in the secretory pathway
Fluhrer, R., Capell, A., Westmeyer, G. G., Willem, M., Hartung, B., Condron, M. M., Teplow, D. B., Haass, C., & Walter, J. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00908.x · Cited by 113 · see citing works
Sequential Amyloid-β Degradation by the Matrix Metalloproteases MMP-2 and MMP-9*
Hernández-Guillamon, M., Mawhirt, S., Blais, S., Montaner, J., Neubert, T., Rostagno, A., & Ghiso, J. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.610931 · Cited by 110 · see citing works
Self-citationRovelet-Lecrux, A., Charbonnier, C., Wallon, D., Nicolas, G., Seaman, M. N. J., Pottier, C., Breusegem, S. Y., Mathur, P. P., Jenardhanan, P., Le Guennec, K., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.100 · Cited by 106 · see citing works
Self-citationPhysiological Functions of the β-Site Amyloid Precursor Protein Cleaving Enzyme 1 and 2
Yan, R. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00097 · Cited by 105 · see citing works
Cognitive markers of preclinical and prodromal Alzheimer's disease in Down syndrome
Startin, C. M., Hamburg, S., Hithersay, R., Al‐Janabi, T., Mok, K. Y., Hardy, J., & Strydom, A. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.08.009 · Cited by 98 · see citing works
Self-citation3D-FISH on Cultured Cells Combined with Immunostaining
Solovei, I. V., & Cremer, M. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-789-1_8 · Cited by 90 · see citing works
Murray, A., Letourneau, A., Canzonetta, C., Stathaki, E., Gimelli, S., Sloan-Bena, F., Abrehart, R., Goh, P., Lim, S., Baldo, C., et al. (2015) · Stem Cells · doi:10.1002/stem.1968 · Cited by 78 · see citing works
Self-citationAβ truncated species: Implications for brain clearance mechanisms and amyloid plaque deposition
Cabrera, E., Mathews, P. M., Mezhericher, E., Beach, T. G., Deng, J., Neubert, T. A., Rostagno, A. A., & Ghiso, J. A. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.07.005 · Cited by 77 · see citing works
Self-citationShi, X.-P., Tugusheva, K., Bruce, J. E., Lucka, A., Wu, G.-X., Chen-Dodson, E., Price, E. A., Li, Y., Xu, M., Huang, Q., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209859200 · Cited by 74 · see citing works
Mann, D. M. A., Davidson, Y. S., Robinson, A. C., Allen, N., Hashimoto, T., Richardson, A., Jones, M., Snowden, J. S., Pendleton, N., Potier, M.-C., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1866-3 · Cited by 73 · see citing works
Self-citationOvchinnikov, D. A., Korn, O., Virshup, I., Wells, C. A., & Wolvetang, E. J. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.05.004 · Cited by 71 · see citing works
Regulation of amyloid precursor protein processing by its KFERQ motif
Park, J., Kim, D., & Yoon, S. (2016) · BMB Reports · doi:10.5483/bmbrep.2016.49.6.212 · Cited by 69 · see citing works
The LonDownS adult cognitive assessment to study cognitive abilities and decline in Down syndrome
Startin, C. M., Hamburg, S., Hithersay, R., Davies, A., Rodger, E., Aggarwal, N., Al‐Janabi, T., & Strydom, A. (2016) · Wellcome Open Research · doi:10.12688/wellcomeopenres.9961.1 · Cited by 67 · see citing works
Self-citationIdentification of BACE2 as an avid ß-amyloid-degrading protease
Abdul‐Hay, S. O., Sahara, T., McBride, M., Kang, D., & Leissring, M. A. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-46 · Cited by 65 · see citing works
BACE2 Expression Increases in Human Neurodegenerative Disease
Holler, C. J., Webb, R. L., Laux, A. L., Beckett, T. L., Niedowicz, D. M., Ahmed, R. R., Liu, Y., Simmons, C. R., Dowling, A. L. S., Spinelli, A., et al. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.09.034 · Cited by 63 · see citing works
Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome
Strydom, A., Heslegrave, A., Startin, C. M., Mok, K. Y., Hardy, J., Groet, J., Nižetić, D., & Zetterberg, H. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0367-x · Cited by 60 · see citing works
Self-citationStockley, J. H., Ravid, R., & O’Neill, C. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.10.076 · Cited by 50 · see citing works
Future Therapeutics in Alzheimer’s Disease: Development Status of BACE Inhibitors
Evin, G. M. (2016) · BioDrugs · doi:10.1007/s40259-016-0168-3 · Cited by 49 · see citing works
Detection of aneuploidies by paralogous sequence quantification
Deutsch, S., Choudhury, U., Merla, G., Howald, C., Sylvan, A., & Antonarakis, S. E. (2004) · Journal of Medical Genetics · doi:10.1136/jmg.2004.023184 · Cited by 49 · see citing works
Polymorphisms in BACE2 may affect the age of onset Alzheimer's dementia in Down syndrome
Mok, K. Y., Jones, E. L., Hanney, M., Harold, D., Sims, R., Williams, J., Ballard, C., & Hardy, J. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.12.022 · Cited by 48 · see citing works
Self-citationSchmued, L. C., Raymick, J. B., Tolleson, W. H., Sarkar, S., Zhang, Y.-H., & Bell-Cohn, A. J. (2012) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2012.05.019 · Cited by 44 · see citing works
Chromosome 21 BACE2 haplotype associates with Alzheimer's disease: A two-stage study
Myllykangas, L., Vrièze, F. W., Polvikoski, T. M., Notkola, I.-L. K., Sulkava, R. O., Niinistö, L., Edland, S. D., Arepalli, S., Adighibe, O., Compton, D., et al. (2005) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2005.04.008 · Cited by 36 · see citing works
Self-citationA promising, novel, and unique BACE1 inhibitor emerges in the quest to prevent Alzheimer's disease
Zakaria, J. A. D., & Vassar, R. J. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201809717 · Cited by 30 · see citing works
Portelius, E., Hölttä, M., Soininen, H. S., Bjerke, M., Zetterberg, H., Westerlund, A., Herukka, S., Blennow, K., & Mattsson, N. (2014) · NeuroMolecular Medicine · doi:10.1007/s12017-014-8302-1 · Cited by 28 · see citing works
Self-citationAzkona, G., Levanon, D., Groner, Y., & Dierssen, M. (2010) · Amino Acids · doi:10.1007/s00726-010-0662-8 · Cited by 24 · see citing works
Holm-Bonferroni Sequential Correction: An EXCEL Calculator - Ver. 1.2
Gaetano, J. (2013) · doi:10.13140/rg.2.1.3920.0481 · Cited by 19 · see citing works
Startin, C. M., Hamburg, S., Hithersay, R., Davies, A., Rodger, E., Aggarwal, N. T., Al‐Janabi, T., & Strydom, A. (2016) · UCL Discovery (University College London) · Cited by 11 · see citing works
Self-citation(2019) · Brain · doi:10.1093/brain/awz061 · Cited by 2 · see citing works
Portelius, E., Holtta, M., Soininen, H., Bjerke, M., Zetterberg, H., Westerlund, A., Herukka, S.-K., Blennow, K., & Mattsson, N. (2014) · UCL Discovery (University College London) · Cited by 1 · see citing works
Self-citation
Flagged first, then by citations
2 of the 64 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Microglia-like Cells Promote Neuronal Functions in Cerebral Organoids
Fagerlund, I., Dougalis, A., Shakirzyanova, A., Gómez‐Budia, M., Pelkonen, A., Konttinen, H., Ohtonen, S., Fazaludeen, M. F., Koskuvi, M., Kuusisto, J., et al. (2021) · Cells · doi:10.3390/cells11010124 · Cited by 124 · see citing works
Barák, M., Fedorová, V., Pospíšilová, V., Raška, J., Vochyánová, S., Sedmík, J., Hříbková, H., Klímová, H., Váňová, T., & Bohačiaková, D. (2022) · Stem Cell Reviews and Reports · doi:10.1007/s12015-021-10254-3 · Cited by 100 · see citing works
The Application of Brain Organoids: From Neuronal Development to Neurological Diseases
Shou, Y., Liang, F., Xu, S., & Li, X. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.579659 · Cited by 86 · see citing works
Váňová, T., Sedmík, J., Raška, J., Černá, K. A., Tauš, P., Pospisilova, V., Nezvedová, M., Fedorová, V., Kadakova, S., Klímová, H., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113310 · Cited by 76 · see citing works
The future of stem cell therapies of Alzheimer’s disease
Wang, Z., Wang, Z.-T., Sun, Y., Tan, L., & Yu, J. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101655 · Cited by 62 · see citing works
Secretases in Alzheimer's disease: Novel insights into proteolysis of APP and TREM2
Lichtenthaler, S. F., Tschirner, S. K., & Steiner, H. (2022) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2021.09.003 · Cited by 60 · see citing works
A beginner’s guide on the use of brain organoids for neuroscientists: a systematic review
Mulder, L., Depla, J. A., Sridhar, A., Wolthers, K. C., Pajkrt, D., & de Sá, R. V. (2023) · Stem Cell Research & Therapy · doi:10.1186/s13287-023-03302-x · Cited by 62 · see citing works
Koriyama, Y., Hori, A., Ito, H., Yonezawa, S., Baba, Y., Tánimoto, N., Ueno, T., Yamamoto, S., Yamamoto, T., Asada, N., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01917 · Cited by 56 · see citing works
Dissecting Alzheimer's disease pathogenesis in human 2D and 3D models
Cenini, G., Hebisch, M., Iefremova, V., Flitsch, L. J., Breitkreuz, Y., Tanzi, R. E., Kim, D. Y., Peitz, M., & Brüstle, O. (2020) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2020.103568 · Cited by 56 · see citing works
Foliaki, S. T., Schwarz, B. H., Groveman, B. R., Walters, R. O., Ferreira, N., Orru, C. D., Smith, A., Wood, A. R., Schmit, O. M., Freitag, P., et al. (2021) · Molecular Brain · doi:10.1186/s13041-021-00864-w · Cited by 59 · see citing works
Boerwinkle, A. H., Gordon, B. A., Wisch, J., Flores, S., Henson, R. L., Butt, O. H., McKay, N., Chen, C. D., Benzinger, T. L. S., Fagan, A. M., et al. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00408-2 · Cited by 55 · see citing works
Venkataraman, L., Fair, S. R., McElroy, C. A., Hester, M. E., & Fu, H. (2020) · Stem Cell Reviews and Reports · doi:10.1007/s12015-020-10068-9 · Cited by 54 · see citing works
Kim, S. W., Woo, H.-J., Kim, E. H., Kim, H. S., Suh, H. N., Kim, S.-H., Song, J. J., Wulansari, N., Kang, M., Choi, S., et al. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102086 · Cited by 56 · see citing works
Becerra-Calixto, A., Mukherjee, A., Ramírez, S., Sepulveda, S. E., Sinha, T., Al‐Lahham, R., Gregorio, N. D., Gherardelli, C., & Soto, C. A. (2023) · Cells · doi:10.3390/cells12040625 · Cited by 54 · see citing works
Chen, X., Salehi, A., Pearn, M. L., Overk, C., Nguyen, P. D., Kleschevnikov, A. M., Maccecchini, M. L., & Mobley, W. C. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12185 · Cited by 54 · see citing works
Impact of increased <i>APP</i> gene dose in Down syndrome and the Dp16 mouse model
Sawa, M., Overk, C., Becker, A., Derse, D., Albay, R., Weldy, K., Salehi, A., Beach, T. G., Doran, E., Head, E., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12463 · Cited by 54 · see citing works
Porciúncula, L. O., Goto‐Silva, L., Ledur, P. F., & Rehen, S. K. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.674563 · Cited by 51 · see citing works
Human iPSC-Based Modeling of Central Nerve System Disorders for Drug Discovery
Lu, Q., & Julia, T. C. W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031203 · Cited by 48 · see citing works
Current progress of cerebral organoids for modeling Alzheimer's disease origins and mechanisms
Sreenivasamurthy, S., Laul, M., Zhao, N., Kim, T., & Zhu, D. (2022) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10378 · Cited by 46 · see citing works
Functional bioengineered models of the central nervous system
Rouleau, N., Murugan, N. J., & Kaplan, D. L. (2023) · Nature Reviews Bioengineering · doi:10.1038/s44222-023-00027-7 · Cited by 46 · see citing works
Visualization of accessible cholesterol using a GRAM domain-based biosensor
Koh, D. H. Z., Naito, T., Na, M., Yeap, Y. J., Rozario, P., Zhong, F. L., Lim, K., & Saheki, Y. (2023) · Nature Communications · doi:10.1038/s41467-023-42498-7 · Cited by 40 · see citing works
Self-citationBACE1 Inhibitors for Alzheimer’s Disease: Current Challenges and Future Perspectives
Coimbra, J. R. M., Resende, R., Custódio, J. B., Salvador, J. A. R., & Santos, A. (2024) · Journal of Alzheimer's Disease · doi:10.3233/jad-240146 · Cited by 33 · see citing works
D’Antoni, C., Mautone, L., Sanchini, C., Tondo, L., Grassmann, G., Cidonio, G., Bezzi, P., Cordella, F., & Angelantonio, S. D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310762 · Cited by 39 · see citing works
Down syndrome and Alzheimer's disease: insights into biomarkers, clinical symptoms, and pathology
Rafii, M. S., Schlachetzki, Z., Barroeta, I., Head, E., Fortea, J., & Ances, B. M. (2025) · The Lancet Neurology · doi:10.1016/s1474-4422(25)00237-6 · Cited by 44 · see citing works
Murray, A., Gough, G., Cindrić, A., Vučković, F., Koschut, D., Borelli, V., Petrović, D. J., Bekavac, A., Plećaš, A., Hribljan, V., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104692 · Cited by 37 · see citing works
Self-citationHe, F., Yu, J., Yang, J., Wang, S., Zhuang, A., Shi, H., Gu, X., Xu, X., Chai, P., & Jia, R. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.02.014 · Cited by 35 · see citing works
Collo, G., Mucci, A., Giordano, G. M., Pich, E. M., & Galderisi, S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00632 · Cited by 33 · see citing works
Wu, C.-I., Vinton, E. A., Pearse, R. V., Heo, K., Aylward, A. J., Hsieh, Y., Bi, Y., Adeleye, S., Fancher, S. B., Duong, D. M., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01454-5 · Cited by 33 · see citing works
Elevated soluble amyloid beta protofibrils in Down syndrome and Alzheimer's disease
Johannesson, M., Sahlin, C., Söderberg, L., Basun, H., Fälting, J. M., Möller, C., Zachrisson, O., Sunnemark, D., Svensson, A., Odergren, T., et al. (2021) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2021.103641 · Cited by 32 · see citing works
Small-molecule BACE1 inhibitors: a patent literature review (2011 to 2020)
Rombouts, F. J. R., Kusakabe, K., Hsiao, C., & Gijsen, H. J. M. (2020) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2021.1832463 · Cited by 31 · see citing works
Fertan, E., Böken, D., Murray, A., Danial, J. S. H., Lam, J. Y. L., Wu, Y., Goh, P. A., Alić, I., Cheetham, M. R., Lobanova, E., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-023-02333-3 · Cited by 31 · see citing works
Self-citationChoroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2
Shaker, M. R., Slonchak, A., Al-mhanawi, B., Morrison, S. D., Sng, J. D. J., Cooper-White, J. J., Khromykh, A. A., & Wolvetang, E. J. (2024) · Science Advances · doi:10.1126/sciadv.adj4735 · Cited by 32 · see citing works
Meijer, L., Chrétien, E., & Ravel, D. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-240078 · Cited by 30 · see citing works
Personalizing the Care and Treatment of Alzheimer’s Disease: An Overview
Štrac, D. Š., Konjevod, M., Šagud, M., Perković, M. N., Erjavec, G. N., Vuić, B., Šimić, G., Vukić, V., Mimica, N., & Pivac, N. (2021) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s284615 · Cited by 29 · see citing works
Self-citationKappel, D. B., Schuch, J. B., Rovaris, D. L., da Silva, B. S., Müller, D., Breda, V., Teche, S. P., Riesgo, R. D. S., Schüler‐Faccini, L., Rohde, L. A., et al. (2019) · NeuroMolecular Medicine · doi:10.1007/s12017-019-08525-x · Cited by 29 · see citing works
Advances in Drug Therapy for Alzheimer’s Disease
Zhu, C.-C., Fu, S., Chen, Y., Li, L., Mao, R., Wang, J., Liu, R., Liu, Y., & Wang, X. (2020) · Current Medical Science · doi:10.1007/s11596-020-2281-2 · Cited by 32 · see citing works
Fujimoto, K., Yoshida, S., Tadano, G., Asada, N., Fuchino, K., Suzuki, S., Matsuoka, E., Yamamoto, T., Yamamoto, S., Ando, S., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01858 · Cited by 29 · see citing works
BACE2 variant identified from HSCR patient causes AD-like phenotypes in hPSC-derived brain organoids
Luo, J., Zou, H., Guo, Y., Huang, K., Ngan, E., & Li, P. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-00845-5 · Cited by 29 · see citing works
Cerebral Organoids as an Experimental Platform for Human Neurogenomics
Nowakowski, T. J., & Salama, S. R. (2022) · Cells · doi:10.3390/cells11182803 · Cited by 26 · see citing works
Martini, A. C., Gross, T. J., Head, E., & Mapstone, M. E. (2022) · Neuron · doi:10.1016/j.neuron.2022.04.001 · Cited by 26 · see citing works
Modeling Alzheimer’s disease using human cell derived brain organoids and 3D models
Fernandes, S., Revanna, J. S., Pratt, J. M., Hayes, N., Marchetto, M. C., & Gage, F. H. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1434945 · Cited by 29 · see citing works
Tosh, J. L., Rhymes, E. R., Mumford, P., Whittaker, H. T., Pulford, L. J., Noy, S. J., Cleverley, K., LonDownS Consortium, Strydom, A., Fisher, E., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-85062-3 · Cited by 26 · see citing works
Self-citationRombouts, F. J. R., Kusakabe, K., Alexander, R., Austin, N. E., Borghys, H., Cleyn, M. A. J. D., Dhuyvetter, D., Gijsen, H. J. M., Hrupka, B. J., Jacobs, T., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00935 · Cited by 26 · see citing works
Interfacing brain organoids with precision medicine and machine learning
Zheng, H., Feng, Y., Tang, J., & Ma, S. (2022) · Cell Reports Physical Science · doi:10.1016/j.xcrp.2022.100974 · Cited by 25 · see citing works
Bhattacharya, A., Choi, W. W. Y., Muffat, J., & Li, Y. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167386 · Cited by 24 · see citing works
BACE2: A Promising Neuroprotective Candidate for Alzheimer’s Disease
Yeap, Y. J., Kandiah, N., Nižetić, D., & Lim, K. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220867 · Cited by 23 · see citing works
Self-citationCerebral Organoids and Antisense Oligonucleotide Therapeutics: Challenges and Opportunities
Lange, J., Zhou, H., & McTague, A. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.941528 · Cited by 22 · see citing works
Genetic Mapping of APP and Amyloid-β Biology Modulation by Trisomy 21
Mumford, P., Tosh, J., Anderle, S., Gkanatsiou Wikberg, E., Lau, G., Noy, S., Cleverley, K., Saito, T., Saido, T. C., Yu, E., et al. (2022) · The Journal of Neuroscience · doi:10.1523/jneurosci.0521-22.2022 · Cited by 22 · see citing works
Self-citationTowards a quality control framework for cerebral cortical organoids
Castiglione, H., Madrange, L., Baquerre, C., Maisonneuve, B. G. C., Lemonnier, T., Deslys, J., Yates, F., Honegger, T., Rontard, J., & Vigneron, P.-A. (2025) · Scientific Reports · doi:10.1038/s41598-025-14425-x · Cited by 21 · see citing works
Ueno, T., Matsuoka, E., Asada, N., Yamamoto, S., Kanegawa, N., Ito, M., Ito, H., Moechars, D., Rombouts, F. J. R., Gijsen, H. J. M., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00359 · Cited by 20 · see citing works
Phenotype and imaging features associated with APP duplications
Grangeon, L., Charbonnier, C., Zaréa, A., Rousseau, S., Rovelet‐Lecrux, A., Bendetowicz, D., Lemaitre, M., Malrain, C., Quillard‐Muraine, M., Cassinari, K., et al. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01172-2 · Cited by 18 · see citing works
Self-citationLuo, J., & Li, P. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00617-1 · Cited by 20 · see citing works
Dolciotti, C., Righi, M., Grecu, E., Trucas, M., Maxia, C., Murtas, D., & Diana, A. (2025) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2025.1553642 · Cited by 18 · see citing works
Licinio, J., & Wong, M. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-01968-6 · Cited by 17 · see citing works
Tripathi, S., Ansari, A. A., Singh, M., Dash, M., Kumar, P., Singh, H., Panda, B., Nukavarapu, S. P., Camci‐Unal, G., Li, B., et al. (2025) · Materials Horizons · doi:10.1039/d5mh00501a · Cited by 18 · see citing works
Cell models for Down syndrome-Alzheimer’s disease research
Wu, Y., West, N. R., Bhattacharyya, A., & Wiseman, F. K. (2022) · Neuronal Signaling · doi:10.1042/ns20210054 · Cited by 17 · see citing works
Self-citationModelling Alzheimer's disease using human brain organoids: current progress and challenges
Yanakiev, M., Soper, O., Berg, D. A., & Kang, E. (2022) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2022.40 · Cited by 16 · see citing works
Gkanatsiou, E., Sahlin, C., Portelius, E., Johannesson, M., Söderberg, L., Fälting, J. M., Basun, H., Möller, C., Odergren, T., Zetterberg, H., et al. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.135894 · Cited by 18 · see citing works
Self-citationExperimental approaches for altering the expression of Abeta‐degrading enzymes
Loeffler, D. A. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15762 · Cited by 18 · see citing works
Wu, Y., Mumford, P., Noy, S., Cleverley, K., Mrzyglod, A., Luo, D., van Dalen, F., Verdoes, M., Fisher, E. M. C., & Wiseman, F. K. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01632-8 · Cited by 16 · see citing works
Self-citationThe Alzheimer’s disease–linked protease BACE2 cleaves VEGFR3 and modulates its signaling
Schmidt, A., Hrupka, B. J., van Bebber, F., Kumar, S. S., Feng, X., Tschirner, S. K., Aßfalg, M., Müller, S. A., Hilger, L. S., Hofmann, L. I., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci170550 · Cited by 16 · see citing works
Silva, A. L. T. E., Yokota-Moreno, B. Y., Sertie, A. L., & Zampieri, B. L. (2023) · Stem Cell Reviews and Reports · doi:10.1007/s12015-022-10497-8 · Cited by 16 · see citing works
Takata, M., Nishimura, K., Harada, K., Iwasaki, R., Ando, M., Yamada, S., Ginhoux, F., & Takata, K. (2023) · Tissue and Cell · doi:10.1016/j.tice.2023.102023 · Cited by 15 · see citing works
Fertan, E., Hung, C., Danial, J. S. H., Lam, J. Y. L., Preman, P., Albertini, G., English, E. A., Böken, D., Livesey, F. J., Strooper, B. D., et al. (2024) · Brain Communications · doi:10.1093/braincomms/fcae454 · Cited by 16 · see citing works
Resistance and resilience to Alzheimer's disease in Down syndrome
Boyle, R. T., Koops, E. A., Ances, B. M., Andrews, E. J., Arenaza‐Urquijo, E. M., Bejanin, A., Brickman, A. M., Buckley, R. F., Clas, G. S., Costello, E., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70151 · Cited by 15 · see citing works
Genetic Signatures of Drug Response Variability inDrosophila melanogaster
Rohde, P. D., Jensen, I. R., Sarup, P. M., Ørsted, M., Demontis, D., Sørensen, P., & Kristensen, T. N. (2019) · Genetics · doi:10.1534/genetics.119.302381 · Cited by 14 · see citing works
Czerminski, J. T., King, O. D., & Lawrence, J. B. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.972201 · Cited by 15 · see citing works
Unterholzner, J., Millischer, V., Wotawa, C., Sawa, A., & Lanzenberger, R. R. (2021) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyab037 · Cited by 15 · see citing works
Microglia Orchestrate Neuronal Activity in Brain OrganoidsPreprint
Fagerlund, I., Dougalis, A., Shakirzyanova, A., Gómez‐Budia, M., Konttinen, H., Ohtonen, S., Fazaludeen, M. F., Koskuvi, M., Kuusisto, J., Hernández, D., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.08.416388 · Cited by 14 · see citing works
Biomarker Testing: Piercing the Fog of Alzheimer’s and Related Dementia
Horgan, D., Nobili, F. M., Teunissen, C. E., Grimmer, T., Mitrečić, D., Ris, L., Pirtošek, Z., Bernini, C., Federico, A., Blackburn, D. J., et al. (2020) · Biomedicine Hub · doi:10.1159/000511233 · Cited by 13 · see citing works
Self-citationArber, C., Alatza, A., Leckey, C. A., Paterson, R. W., Zetterberg, H., & Wray, S. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15315 · Cited by 12 · see citing works
Self-citationRegenerative Neurology and Regenerative Cardiology: Shared Hurdles and Achievements
Mitrečić, D., Hribljan, V., Jagečić, D., Isaković, J., Lamberto, F., Horánszky, A., Zana, M., Földes, G., Zavan, B., Pivoriūnas, A., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020855 · Cited by 13 · see citing works
Self-citationDoes Dementia Have a Microbial Cause?
Landry, R. L., & Embers, M. E. (2022) · NeuroSci · doi:10.3390/neurosci3020019 · Cited by 12 · see citing works
Current Development of iPSC-Based Modeling in Neurodegenerative Diseases
Guo, X., Wang, X., Wang, J., Ma, M., & Ren, Q. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26083774 · Cited by 14 · see citing works
Yin, C., Tang, X., Zeng, J., Wang, Z., Mi, J., Liang, Y. J., Qin, D., Feng, Q., & Wu, A. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102954 · Cited by 12 · see citing works
McInvale, J. J., Canoll, P., & Hargus, G. (2024) · Brain Pathology · doi:10.1111/bpa.13231 · Cited by 11 · see citing works
BACE1 as an early biomarker and its relevance to risk factors for Alzheimer’s disease
Ohno, M. (2025) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2025.111475 · Cited by 12 · see citing works
Dierssen, M., Hérault, Y., Helguera, P. R., de Lagrán, M. M., Vázquez, A. V., Christian, B. T., Carmona‐Iragui, M., Wiseman, F. K., Mobley, W. C., Fisher, E., et al. (2021) · Molecular Syndromology · doi:10.1159/000514437 · Cited by 11 · see citing works
Self-citationNeural lineage differentiation of human pluripotent stem cells: Advances in disease modeling
Yan, Y.-W., Qian, E. S., Woodard, L. E., & Bejoy, J. (2023) · World Journal of Stem Cells · doi:10.4252/wjsc.v15.i6.530 · Cited by 11 · see citing works
Farrell, C., Buhidma, Y., Mumford, P., Heywood, W. E., Hällqvist, J., Flores-Aguilar, L., Andrews, E. J., Rahimzadah, N., Taso, O. S., Doran, E., et al. (2025) · Acta Neuropathologica · doi:10.1007/s00401-025-02889-0 · Cited by 9 · see citing works
“…in preclinical models demonstrates that genes other than APP being in three copies modify aspects of DSAD, such as cognition and amyloid-β load [1, 50, 70], but more work is required to understand how the molecular processes of AD are altered by trisomy 21 in the brain of people with DS.…”
Self-citationOhno, M. (2023) · Frontiers in Dementia · doi:10.3389/frdem.2023.1161875 · Cited by 9 · see citing works
He, T., d’Uscio, L. V., & Katušić, Z. S. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15929 · Cited by 9 · see citing works
Guan, D., Sun, S., Song, L., Zhao, P., Nie, Y., Huang, X., Zhou, W., Li, Y., Lei, Y., Hu, Y., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2317430121 · Cited by 9 · see citing works
Ehn, E., Eisfeldt, J., Laffita‐Mesa, J. M., Thonberg, H., Schoumans, J., Portaankorva, A. M., Viitanen, M. H., Lindstrand, A., Nennesmo, I., & Graff, C. (2025) · Scientific Reports · doi:10.1038/s41598-025-86645-0 · Cited by 9 · see citing works
Three-dimensional cell culture technologies in the study of Alzheimer’s disease: a narrative review
Chacón, P. E. A., Irineo‐Moreno, V., & Loera‐Valencia, R. (2025) · Advanced technology in neuroscience . · doi:10.4103/atn.atn-d-24-00016 · Cited by 6 · see citing works
Three-dimensional human brain organoids: A next-generation model to decode Alzheimer’s disease
Kumari, S., Ashvin, Dhapola, R., Sharma, P., Paidlewar, M., Vellingiri, B., Medhi, B., & HariKrishnaReddy, D. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102928 · Cited by 6 · see citing works
Single-cell atlas of the developing Down syndrome brain cortex
Lattke, M., Tan, W. L., Sukumaran, S. K., Utami, K. H., Sintes, M., Sakthivel, S., Tan, J., Lim, A. T. J., Bansal, V. A., Rekopoulou, K., et al. (2026) · Nature Medicine · doi:10.1038/s41591-026-04211-1 · Cited by 8 · see citing works
Self-citationPereira, M. F., Shyti, R., & Testa, G. (2024) · Stem Cell Reports · doi:10.1016/j.stemcr.2024.05.004 · Cited by 6 · see citing works
Biological Mechanism-based Neurology and Psychiatry: A BACE1/2 and Downstream Pathway Model
Hampel, H. J., Lista, S., Caruso, G., Nisticò, R., Piccioni, G., Mercuri, N. B., Giorgi, F. S., Ferrarelli, F., Lemercier, P., Caraci, F., et al. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666211201095701 · Cited by 6 · see citing works
A Comprehensive Update of Cerebral Organoids between Applications and Challenges
Li, X., Shopit, A., & Wang, J. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/7264649 · Cited by 6 · see citing works
Dannert, A., Schulz, N., Klimmt, J., Knez, L., Groschup, B., Gonçalves, C. C., Carraro, C., Schifferer, M., Brendel, M., & Paquet, D. (2026) · Science Translational Medicine · doi:10.1126/scitranslmed.adu9845 · Cited by 6 · see citing works
Molecular Psychiatry special issue: advances in Alzheimer’s disease
Licinio, J., & Wong, M. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01434-1 · Cited by 5 · see citing works
Ohno, M. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-231451 · Cited by 5 · see citing works
Coronel, R., González-Sastre, R., Mateos-Martínez, P., Maeso, L., Llorente-Beneyto, E., Martín-Benito, S., Gagosian, V. S. C., Foti, L., González, M. D. C., López-Alonso, V., et al. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-01639 · Cited by 5 · see citing works
Schill, D. J., Attili, D., DeLong, C. J., McInnis, M. G., Johnson, C. N., Murphy, G. G., & O’Shea, K. S. (2024) · Cells · doi:10.3390/cells13141194 · Cited by 4 · see citing works
Cindrić, A., Vučković, F., Murray, A., Klarić, T., Alić, I., Petrović, D. J., Krištić, J., Nižetić, D., & Lauc, G. (2024) · BBA Advances · doi:10.1016/j.bbadva.2024.100137 · Cited by 4 · see citing works
Self-citationSynaptic and intrinsic membrane defects disrupt early neural network dynamics in Down syndrome
Hannan, S. B., Alić, I., Murray, A., Kwon, J., Mortensen, M., Kang, H. J., Plećaš, A., Goh, P. A., O’Brien, N. L., Naud, R., et al. (2026) · Nature Communications · doi:10.1038/s41467-025-68048-x · Cited by 3 · see citing works
Self-citationBioengineering of brain organoids: Advancements and challenges
Gopurappilly, R., & Pal, R. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-824064-9.00002-2 · Cited by 3 · see citing works
It’s good to know what to BACE the specificity of your inhibitors on
Murray, A., Muñiz-García, A., Alić, I., & Nižetić, D. (2024) · Journal of Clinical Investigation · doi:10.1172/jci183677 · Cited by 3 · see citing works
Self-citationBorgognone, A., Casadellà, M., de Lagrán, M. M., Paredes, R., Clotet, B., Dierssen, M., & Elizalde‐Torrent, A. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1386944 · Cited by 3 · see citing works
- Authors
- Alić, I., Goh, P. A., Murray, A., Portelius, E., Gkanatsiou, E., Gough, G., Mok, K. Y., Koschut, D., Brunmeir, R., Yeap, Y. J., O’Brien, N. L., Groet, J., Shao, X., Havlicek, S., Dunn, N. R., Kvartsberg, H., Brinkmalm, G., Hithersay, R., Startin, C., Hamburg, S., Phillips, M., Pervushin, K., Turmaine, M., Wallon, D., Rovelet-Lecrux, A., Soininen, H., Volpi, E., Martin, J. E., Foo, J. N., Becker, D. L., Rostagno, A., Ghiso, J., Krsnik, Ž., Šimić, G., Kostović, I., Mitrečić, D., LonDownS Consortium, Strydom, A., Fisher, E., Wiseman, F., Nizetic, D., Hardy, J., Tybulewicz, V., Karmiloff-Smith, A., Francis, P. T., Blennow, K., Strydom, A., Hardy, J., Zetterberg, H., & Nižetić, D.
- Affiliations
- Queen Mary University of London (GB)
- Nanyang Technological University (SG)
- University of Gothenburg (SE)
- UCL Queen Square Institute of Neurology (GB)
- Agency for Science, Technology and Research (SG)
- King's College London (GB)
- University College London (GB)
- Inserm (FR)
- University of Eastern Finland (FI)
- University of Westminster (GB)
- New York University (US)
- University of Zagreb (HR)
- The Francis Crick Institute (GB)
- ORCID
- Alić, Ivan
- Goh, Pollyanna A.
- Murray, Aoife
- Portelius, Erik
- Gkanatsiou, Eleni
- Gough, Gillian
- Mok, Kin Y.
- Koschut, David
- Brunmeir, Reinhard
- Yeap, Yee Jie
- O’Brien, Niamh L.
- Shao, Xiaowei
- Dunn, N. Ray
- Kvartsberg, Hlin
- Brinkmalm, Gunnar
- Hithersay, Rosalyn
- Startin, Carla
- Hamburg, Sarah
- Pervushin, Konstantin
- Wallon, David
- Soininen, Hilkka
- Volpi, Emanuela
- Martin, Joanne E.
- Foo, Jia Nee
- Becker, David L.
- Rostagno, Agueda
- Ghiso, Jorge
- Krsnik, Željka
- Šimić, Goran
- Kostović, Ivica
- Mitrečić, Dinko
- Fisher, Elizabeth
- Wiseman, Frances
- Tybulewicz, Victor
- Francis, Paul T.
- Blennow, Kaj
- Zetterberg, Henrik
- Nižetić, Dean
- Venue
- Molecular Psychiatry
- Published
- 2020-07-10
- Volume
- 26
- Issue
- 10
- Pages
- 5766-5788
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC8190957
- OpenAlex
- W3041871366
- Cited by
- 123
- References
- 64
- Citations by year
- 2026: 9 · 2025: 22 · 2024: 16 · 2023: 21 · 2022: 20 · 2021: 24 · 2020: 9 · 2019: 2
- FWCI
- 11.73
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-07-16)
- Open access
- hybrid
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
- WestminsterResearch (University of Westminster) (submittedVersion, cc-by)
- The Francis Crick Institute (cc-by)
- Funders
- BrightFocus Foundation (A2015275S)
- Wellcome Trust (FP7/2007–2013, 098330, 608765, 098330/Z/12/Z, 217199, 217199/Z/19/Z, 098327/Z/12/Z)
- Francis Crick Institute (10194)
- EU Joint Programme – Neurodegenerative Disease Research
- Alzheimer's Society
- Zaklade Adris
- Parkinson's UK (G-0907)
- European Commission (608765, GA KK 01 1 1 01 0007, 2007–2013, FP7 2007-2013, FP7/2007, IP-2019-04-3584)
- Rosetrees Trust
- National Research Foundation (NRF-NRFF2016-03)
- National Research Foundation Singapore (NRFF2016, NRF-NRFF2016-03)
- Agence Nationale de la Recherche (ANR-17-JPCD-0003)
- Royal Swedish Academy of Sciences (2017-00915)
- Fondation pour la Recherche Médicale
- Hjärnfonden (FO2017‑0243, FO2017, ALFGBG-715986)
- Vetenskapsrådet (FP7/2007-2013, 2017-00915, (#ALFGBG-715986, ALFGBG-720931, FO2017-0243)
- Hrvatska Zaklada za Znanost (IP-2019-04, IP-2016-06-9451, PZS-2019-02-4277, IP-2019-04-3584, GA KK01.1.1.01.0007, KK01.1.1.01.0007, 2019‐04‐3584)
- UK Dementia Research Institute (#2017-00915, ALFGBG-715986, FO2017-0243, -0243, -715986)
- National Institutes of Health (IP-2019-04-3584, FP7/2007-2013, 1rf1ag059695-01a1, KK.01.1.1.01.0007, GA KK01.1.1.01.0007)
- Medical Research Council (FP7/20072013, MR/L501542/1, MR/S011277/1, MR/R024901/1, MR/N026004/1, 608765, MR/T002581/1)
- National Medical Research Council (NMRC/CIRG/1438/ 2015)
- European Regional Development Fund (GA KK01.1.1.01.0007, FP7/2007‐2013, 2007 – 2013, KK.01.1.1.01.0007, IP-2019-04-3584)
- National Institute on Aging (RF1 AG059695)
- 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, Alzheimer's disease, BACE2, brain organoids, amyloid-beta, tau hyperphosphorylation, BACE1 inhibitors, gene dosage, beta-secretase inhibition, gamma-secretase inhibition, cerebrospinal fluid biomarkers, neurodegeneration, drug screening
- MeSH terms
- Alzheimer Disease, Brain, Down Syndrome, Humans, Organoids, Trisomy, Genes, Suppressor, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Amyloid Precursor Protein Secretases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
