Consequences of trisomy 21 for brain development in Down syndrome

In the paper

“Several studies have shown that fewer interneurons are present in the cortex of individuals with DS44,46,84 than in that of controls, suggesting that reduced generation of interneurons contributes to the overall reduced neurogenesis in DS.”

What the sources say

• Disputed

  Split into 2 atoms — 0 confirmed, 0 partially supported, 2 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Checked by a reasoning model — may be wrong.

  cites [44] Guidi, S. et al. Abnormal development of the inferior temporal region in fetuses with Down syndrome. Brain Pathol. 28, 986–998 (2018). This study reveals reduced thickness and fewer neurons in the fusiform and temporal gyrus of fetuses with Down syndrome than in those of controls. sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [46] Ross, M. H., Galaburda, A. M. & Kemper, T. L. Down’s syndrome: is there a decreased population of neurons? Neurology 34, 909–916 (1984). In a small sample size of whole-brain sections, this research has observed fewer granular, presumably aspinous stellate, neurons in Down syndrome brains than in controls. source
• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [84] Giffin-Rao, Y. et al. Altered patterning of trisomy 21 interneuron progenitors. Stem Cell Rep. 17, 1366–1379 (2022). sourceExperimental — accuracy not yet measured

In the paper

“Although these models come with their own limitations, including variability and limited functional maturation (Box 1), the differentiation of iPSCs into neural cells recapitulates many of the neurodevelopmental features observed in prenatal human tissue and occurs in a temporal sequence that roughly corresponds to in vivo corticogenesis29–31.”

What the sources say

• Partly supported

  The Challenges and future directions sections say hPSC neural differentiation mirrors in vivo development and that derived neurons resemble fetal-brain neurons in gene-expression profiles. The subtype-progenitor section describes a cortical sequence matching development, but its stem-cell example uses mouse ESCs; it does not establish that human iPSC-derived cortical cells follow that sequence. (LLM, conf=0.83)

  cites [29] Tao, Y. & Zhang, S. C. Neural subtype specification from human pluripotent stem cells. Cell Stem Cell 19, 573–586 (2016). sourceExperimental — accuracy not yet measured
• Partly supported

  The Phenotypic analysis of CNS and cortical neuron identity section (page unavailable) reports successive waves of cell birth and a temporal order of cortical-layer marker expression consistent with in vivo corticogenesis. It does not establish the broader claim that the cultures recapitulate many features observed in prenatal human tissue. (LLM, conf=0.84)

  cites [30] Qi, Y. et al. Combined small-molecule inhibition accelerates the derivation of functional cortical neurons from human pluripotent stem cells. Nat. Biotechnol. 35, 154–163 (2017). sourceExperimental — accuracy not yet measured
• Supported

  In “Generation of excitatory projection neurons from hPSCs” (page unavailable), the review says a cortical differentiation method reproduced progenitor populations seen in the developing human brain and produced cortical neurons in a temporal pattern paralleling in vivo corticogenesis. In “Deriving neurons from hPSCs to model neurodevelopmental disorders” (page unavailable), it reports a close expression-profile similarity to human frontal cortex at 8–10 weeks post-conception. (LLM, conf=0.90)

  cites [31] Kim, D. S., Ross, P. J., Zaslavsky, K. & Ellis, J. Optimizing neuronal differentiation from induced pluripotent stem cells to model ASD. Front. Cell Neurosci. 8, 109 (2014). source

In the paper

“These cognitive and brain structure deficits emerge as early as 6 months of age and progress to have substantial impacts on daily life, as well as academic and occupational outcomes5–7.”

What the sources say

• ?Not checked — no full text of the sourcecites [5] Fidler, D. J., Hepburn, S. L., Mankin, G. & Rogers, S. J. Praxis skills in young children with Down syndrome, other developmental disabilities, and typically developing children. Am. J. Occup. Ther. 59, 129–138 (2005). source
• Partly supported

  The Introduction describes cognitive weaknesses in Down syndrome, and the Discussion reports brain-volume differences in neonates. The paper does not establish that cognitive deficits emerge at six months or that these deficits progress to affect daily life, academic outcomes, and occupational outcomes; its Conclusion says the link between neonatal brain development and later outcomes remains unclear. No page numbers were available in our copy. (LLM, conf=0.86)

  cites [6] Fukami-Gartner, A. et al. Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome. Cereb. Cortex 33, 8921–8941 (2023). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [7] Pinter, J. D., Eliez, S., Schmitt, J. E., Capone, G. T. & Reiss, A. L. Neuroanatomy of Down’s syndrome: a high-resolution MRI study. Am. J. Psychiatry 158, 1659–1665 (2001). This high-resolution MRI study confirms that volumetric brain differences occur at early ages in Down syndrome. source

In the paper

“Interestingly, in one study, when neurons were generated from T21 and euploid iPSCs through directed differentiation, no significant differences in neuron production between genotypes were detected, but when the same cell lines were allowed to spontaneously differentiate, the trisomic lines produced a significantly decreased percentage of neurons82.”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [82] 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). This study identifies a role for astrocytes in regulating neuronal function in Down syndrome pathogenesis using trisomy 21 iPSC-derived neurons and astrocytes in co-cultures, drug treatment and chimeric mouse brains. source

In the paper

“Together, the presence of fewer cycling cells and the reduced number of progenitors both support the suggestion that neurogenesis is reduced during development in DS, although these data do not distinguish between slower progenitor proliferation or premature progenitor cell cycle exit.”

What the sources say

• ?Not checked — no full text of the sourcecites [40] Contestabile, A. et al. Cell cycle alteration and decreased cell proliferation in the hippocampal dentate gyrus and in the neocortical germinal matrix of fetuses with Down syndrome and in Ts65Dn mice. Hippocampus 17, 665–678 (2007). source
• ?Not checked — no full text of the sourcecites [42] Guidi, S. et al. Neurogenesis impairment and increased cell death reduce total neuron number in the hippocampal region of fetuses with Down syndrome. Brain Pathol. 18, 180–197 (2008). source
• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [43] Guidi, S., Ciani, E., Bonasoni, P., Santini, D. & Bartesaghi, R. Widespread proliferation impairment and hypocellularity in the cerebellum of fetuses with Down syndrome. Brain Pathol. 21, 361–373 (2011). source
• Partly supported

  Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  cites [44] Guidi, S. et al. Abnormal development of the inferior temporal region in fetuses with Down syndrome. Brain Pathol. 28, 986–998 (2018). This study reveals reduced thickness and fewer neurons in the fusiform and temporal gyrus of fetuses with Down syndrome than in those of controls. sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [47] Stagni, F. et al. Subicular hypotrophy in fetuses with Down syndrome and in the Ts65Dn model of Down syndrome. Brain Pathol. 29, 366–379 (2019). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [50] Stagni, F., Giacomini, A., Emili, M., Guidi, S. & Bartesaghi, R. Neurogenesis impairment: an early developmental defect in Down syndrome. Free Radic. Biol. Med. 114, 15–32 (2018). source
• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [64] Stagni, F. et al. Neuroanatomical alterations in higher-order thalamic nuclei of fetuses with Down syndrome. Clin. Neurol. Neurosurg. 194, 105870 (2020). sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [11] Baburamani, A. A. et al. Assessment of radial glia in the frontal lobe of fetuses with Down syndrome. Acta Neuropathol. Commun. 8, 141 (2020). sourceExperimental — accuracy not yet measured

In the paper

“The fetal cortex, cerebellum and hippocampus have all been shown to contain fewer neurons in individuals with DS than in controls40–48, albeit based on small sample sizes17.”

What the sources say

• ?Not checked — no full text of the sourcecites [40] Contestabile, A. et al. Cell cycle alteration and decreased cell proliferation in the hippocampal dentate gyrus and in the neocortical germinal matrix of fetuses with Down syndrome and in Ts65Dn mice. Hippocampus 17, 665–678 (2007). source
• ?Not checked — no full text of the sourcecites [41] Golden, J. A. & Hyman, B. T. Development of the superior temporal neocortex is anomalous in trisomy 21. J. Neuropathol. Exp. Neurol. 53, 513–520 (1994). This analysis of stereological cell counts performed in one neocortical area during gestation in normal development and in trisomy 21 suggests that the emergence of lamination is disrupted in trisomy 21. source
• ?Not checked — no full text of the sourcecites [42] Guidi, S. et al. Neurogenesis impairment and increased cell death reduce total neuron number in the hippocampal region of fetuses with Down syndrome. Brain Pathol. 18, 180–197 (2008). source
• Supported

  The Discussion reports fewer cerebellar granule cells and Purkinje cells in fetuses with Down syndrome than in controls. The Introduction also describes prior evidence of hypocellularity and reduced neurogenesis in cortical and hippocampal regions; this paper does not itself measure neurons in all three regions. The Methods report a small sample of seven Down syndrome fetuses and six controls. (LLM, conf=0.91)

  cites [43] Guidi, S., Ciani, E., Bonasoni, P., Santini, D. & Bartesaghi, R. Widespread proliferation impairment and hypocellularity in the cerebellum of fetuses with Down syndrome. Brain Pathol. 21, 361–373 (2011). source
• Partly supported

  The section ‘Abnormal architecture and reduced neuron number in the FG and ITG of DS fetuses’ reports fewer neurons in two cortical regions and describes a previously reported reduction in the fetal hippocampal region. The Subjects section reports six DS and six euploid fetuses. Our copy does not establish the claimed reduction in the cerebellum, so this source supports only part of the three-region statement. (LLM, conf=0.88)

  cites [44] Guidi, S. et al. Abnormal development of the inferior temporal region in fetuses with Down syndrome. Brain Pathol. 28, 986–998 (2018). This study reveals reduced thickness and fewer neurons in the fusiform and temporal gyrus of fetuses with Down syndrome than in those of controls. sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [45] Larsen, K. B. et al. Reduced cell number in the neocortical part of the human fetal brain in Down syndrome. Ann. Anat. 190, 421–427 (2008). This analysis of stereological cell counts reveals that the total cell number in the neocortex of fetal Down syndrome forebrain is smaller than that of controls. source
• ?Not checked — no full text of the sourcecites [46] Ross, M. H., Galaburda, A. M. & Kemper, T. L. Down’s syndrome: is there a decreased population of neurons? Neurology 34, 909–916 (1984). In a small sample size of whole-brain sections, this research has observed fewer granular, presumably aspinous stellate, neurons in Down syndrome brains than in controls. source
• Supported

  The Results report a lower percentage of neurons in the subiculum of fetuses with Down syndrome than in euploid controls. The paper identifies the subiculum as part of the hippocampal region, supporting the hippocampal finding for which this study is cited. The small-sample qualifier has a separate citation in the citing sentence. (LLM, conf=0.90)

  cites [47] Stagni, F. et al. Subicular hypotrophy in fetuses with Down syndrome and in the Ts65Dn model of Down syndrome. Brain Pathol. 29, 366–379 (2019). source
• ?Not checked — no full text of the sourcecites [48] Wisniewski, K. E., Laure-Kamionowska, M. & Wisniewski, H. M. Evidence of arrest of neurogenesis and synaptogenesis in brains of patients with Down’s syndrome. N. Engl. J. Med. 311, 1187–1188 (1984). This morphometric analysis of the cortex (from birth to 14 years) shows 20% to 50% fewer neurons in Down syndrome brain than in controls from birth. source
• Supported

  Citation 17 is attached to the small-sample-size qualification, rather than to the findings for each brain region. The Discussion (Summary) says many reports had limited sample sizes and few Down syndrome samples; the Results (Synthesis of Findings From Analyzed Studies) likewise cautions that the studies were limited by small numbers or samples. (LLM, conf=0.93)

  cites [17] Risgaard, K. A., Sorci, I. A., Mohan, S. & Bhattacharyya, A. Meta-analysis of Down syndrome cortical development reveals underdeveloped state of the science. Front. Cell Neurosci. 16, 915272 (2022). source

In the paper

“Neurospheres derived from individuals with DS expand more slowly than those from controls, suggesting that they contain fewer proliferating progenitor cells.”

What the sources say

• Partly supported

  In “Characterization of human DS NPCs” (page unavailable), the paper reports that Down syndrome neurospheres appeared to proliferate more slowly than controls shortly after dissociation. It does not establish that they contained fewer proliferating progenitor cells; the same section says the Down syndrome cells generally showed increased proliferation with serial passaging. (LLM, conf=0.86)

  cites [66] Esposito, G. et al. Genomic and functional profiling of human Down syndrome neural progenitors implicates S100B and aquaporin 4 in cell injury. Hum. Mol. Genet. 17, 440–457 (2008). sourceExperimental — accuracy not yet measured
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [67] Lu, J., Delli-Bovi, L. C., Hecht, J., Folkerth, R. & Sheen, V. L. Generation of neural stem cells from discarded human fetal cortical tissue. J. Vis. Exp. 25, 2681 (2011).
• Partly supported

  In “Temporal Changes in Neurogenesis from Trisomy 21 hNPCs,” the paper reports slower growth of trisomy 21 neurospheres and suggests a loss of progenitor cells. It does not establish that fewer of those cells were proliferating: Ki67 measurements found no significant difference in cell division compared with controls. (LLM, conf=0.87)

  cites [68] Bhattacharyya, A., McMillan, E., Chen, S. I., Wallace, K. & Svendsen, C. N. A critical period in cortical interneuron neurogenesis in Down syndrome revealed by human neural progenitor cells. Dev. Neurosci. 31, 497–510 (2009). sourceExperimental — accuracy not yet measured
• Supported

  In “Impaired proliferation in DS HNPs” (Fig. 1C), Down syndrome neurospheres were 40% smaller after one week of expansion and had approximately threefold lower Ki67 or BrdU labeling than controls. These findings support slower expansion and fewer proliferating progenitor cells. (LLM, conf=0.93)

  cites [69] Lu, J. et al. OLIG2 over-expression impairs proliferation of human Down syndrome neural progenitors. Hum. Mol. Genet. 21, 2330–2340 (2012). source

In the paper

“However, results from these studies are discordant: the generation of neurons from iPSCs has been reported in some studies to be impaired74,77–79 and in others not to be impaired75,80,81, which may be explained by technical differences in the cell lines and protocols used (see Box 1).”

What the sources say

• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [74] Li, Z. et al. Asynchronous excitatory neuron development in an isogenic cortical spheroid model of Down syndrome. Front. Neurosci. 16, 932384 (2022). sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  cites [77] Tang, X. Y. et al. DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome. J. Clin. Invest. 131, 135763 (2021). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [78] Lu, H. E. et al. Modeling neurogenesis impairment in Down syndrome with induced pluripotent stem cells from trisomy 21 amniotic fluid cells. Exp. Cell Res. 319, 498–505 (2013). source
• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [79] 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). sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [75] Murray, A. et al. Brief report: isogenic induced pluripotent stem cell lines from an adult with mosaic Down syndrome model accelerated neuronal ageing and neurodegeneration. Stem Cell 33, 2077–2084 (2015). sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [80] Shi, Y. et al. A human stem cell model of early Alzheimer’s disease pathology in Down syndrome. Sci. Transl. Med. 4, 124ra129 (2012). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [81] Weick, J. P. et al. Deficits in human trisomy 21 iPSCs and neurons. Proc. Natl Acad. Sci. USA 110, 9962–9967 (2013). source

In the paper

“Neurogenesis starts at approximately post-conceptional day 50 in the human cortex25,51.”

What the sources say

• Supported

  In “Neuronal generation and migration,” the paper states that neocortical cells begin generating the earliest cortical-plate neurons at approximately 50–51 post-conceptional days. It also gives 48 pcd as the predicted start of neocortical neurogenesis, consistent with the claim’s approximate timing. (LLM, conf=0.93)

  cites [25] Silbereis, J. C., Pochareddy, S., Zhu, Y., Li, M. & Sestan, N. The cellular and molecular landscapes of the developing human central nervous system. Neuron 89, 248–268 (2016). This comprehensive review highlights the molecular and cellular processes of the developing human CNS, with focus on the cerebral neocortex. source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [51] Bayer, S. A., and Altman, J. Atlas of Human Central Nervous System Development Vols 1–5 (Taylor and Francis, 2007).

In the paper

“Interneurons are generated from progenitors located in the ventral forebrain in transient structures called ganglionic eminences and migrate tangentially to the cortex through different migratory streams85–87.”

What the sources say

• ?Not checked — no full text of the sourcecites [85] Anderson, S. A., Eisenstat, D. D., Shi, L. & Rubenstein, J. L. Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science 278, 474–476 (1997). source
• Partly supported

  The Introduction says cortical interneurons arise from progenitors in the embryonic subpallium and migrate tangentially via several streams. The sections on spatial specification and tangential migration support ganglionic-eminence origins and distinct routes, but also identify the preoptic region—separate from the ganglionic eminences—as a source of cortical interneurons. No page numbers are provided in our copy. (LLM, conf=0.84)

  cites [86] Lim, L., Mi, D., Llorca, A. & Marin, O. Development and functional diversification of cortical interneurons. Neuron 100, 294–313 (2018). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [87] Wamsley, B. & Fishell, G. Genetic and activity-dependent mechanisms underlying interneuron diversity. Nat. Rev. Neurosci. 18, 299–309 (2017). source

In the paper

“Altered development of the cortex in DS includes both reduced neurogenesis early in development and altered gliogenesis and myelination later in development39 (Fig. 2).”

What the sources say

• Partly supported

  The Results (no page given) report altered oligodendrocyte differentiation and reduced myelination in the developing Down syndrome neocortex, supporting the later-development part of the claim. The Introduction (no page given) mentions neurogenesis defects in mouse models, but does not establish reduced early neurogenesis in the human cortex; the findings also concern oligodendrocytes rather than gliogenesis broadly. (LLM, conf=0.86)

  cites [39] Olmos-Serrano, J. L. et al. Down syndrome developmental brain transcriptome reveals defective oligodendrocyte differentiation and myelination. Neuron 89, 1208–1222 (2016). This multi-region transcriptome analysis of Down syndrome and euploid control brains spanning from mid-fetal development to adulthood identifies temporal and spatial genome-wide alterations associated with distinct biological processes. sourceExperimental — accuracy not yet measured

In the paper

“This transcriptomic (microarray) investigation of the cortex and cerebellum of individuals with DS from prenatal stages to adulthood has found genome-wide alterations in the expression of a large number of genes (see Box 3), many of which exhibited temporal and spatial specificity and were associated with distinct biological processes, including metabolism (Box 4).”

What the sources say

• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [39] Olmos-Serrano, J. L. et al. Down syndrome developmental brain transcriptome reveals defective oligodendrocyte differentiation and myelination. Neuron 89, 1208–1222 (2016). This multi-region transcriptome analysis of Down syndrome and euploid control brains spanning from mid-fetal development to adulthood identifies temporal and spatial genome-wide alterations associated with distinct biological processes. sourceExperimental — accuracy not yet measured

In the paper

“Evidence of altered regulation of neuronal differentiation genes during the period of neurogenesis is consistent with increased neuronal differentiation, which would suggest premature cell cycle exit39.”

What the sources say

• Partly supported

  The Results section on co-dysregulation reports altered gene-expression modules associated with neuronal differentiation (M4 and M45). It does not establish that these changes occurred specifically during neurogenesis, indicate increased neuronal differentiation, or suggest premature cell-cycle exit. No page number is available in our copy. (LLM, conf=0.83)

  cites [39] Olmos-Serrano, J. L. et al. Down syndrome developmental brain transcriptome reveals defective oligodendrocyte differentiation and myelination. Neuron 89, 1208–1222 (2016). This multi-region transcriptome analysis of Down syndrome and euploid control brains spanning from mid-fetal development to adulthood identifies temporal and spatial genome-wide alterations associated with distinct biological processes. sourceExperimental — accuracy not yet measured

In the paper

“This suggested that cell cycle dynamics are altered in DS and that they are altered differentially at different developmental stages.”

What the sources say

• Supported

  The Results section, “Human down syndrome cells displayed abnormal cell cycle during neural differentiation,” reports reduced proliferation of DS cells early in the neurogenic stage but increased proliferation late in that stage. It also describes a reversal in S-phase occupancy over time, supporting the claim that cell-cycle dynamics differ across developmental stages. (LLM, conf=0.94)

  cites [65] Sharma, V. et al. Biphasic cell cycle defect causes impaired neurogenesis in Down syndrome. Front. Genet. 13, 1007519 (2022). This paper shows that human trisomy 21 iPSCs display abnormal cell cycle features during neural differentiation compared to controls. source

In the paper

“Although therapeutic targeting of this altered excitation–inhibition ratio proved successful in treating cognitive deficits in mice, similar strategies did not prove efficacious for the treatment of intellectual disability in individuals with DS130.”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [130] Goeldner, C. et al. A randomized, double-blind, placebo-controlled phase II trial to explore the effects of a GABAA-α5 NAM (basmisanil) on intellectual disability associated with Down syndrome. J. Neurodev. Disord. 14, 10 (2022). source

In the paper

“The reduced capacity for LTP is driven by increased GABAergic neurotransmission in these animals, and pharmacological reduction of GABAergic neurotransmission is sufficient to rescue this LTP phenotype127–129.”

What the sources say

• ?Not checked — no full text of the sourcecites [127] Kurt, M. A., Kafa, M. I., Dierssen, M. & Davies, D. C. Deficits of neuronal density in CA1 and synaptic density in the dentate gyrus, CA3 and CA1, in a mouse model of Down syndrome. Brain Res. 1022, 101–109 (2004). source
• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [128] Martinez-Cue, C., Delatour, B. & Potier, M. C. Treating enhanced GABAergic inhibition in Down syndrome: use of GABA α5-selective inverse agonists. Neurosci. Biobehav. Rev. 46, 218–227 (2014). source
• ?Could not verify

  Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

  cites [129] Potier, M. C., Braudeau, J., Dauphinot, L. & Delatour, B. Reducing GABAergic inhibition restores cognitive functions in a mouse model of Down syndrome. CNS Neurol. Disord. Drug Targets 13, 8–15 (2014). sourceExperimental — accuracy not yet measured

In the paper

“Synaptogenesis begins in the developing cortex at approximately 18 post-conception weeks (PCW), but dendritic spines — the primary sites of excitatory synaptic contact — do not emerge until about 24 PCW112–114.”

What the sources say

• ?Not checked — no full text of the sourcecites [112] Huttenlocher, P. R. Synaptic density in human frontal cortex — developmental changes and effects of aging. Brain Res. 163, 195–205 (1979). source
• ?Not checked — no full text of the sourcecites [113] Huttenlocher, P. R. & Dabholkar, A. S. Regional differences in synaptogenesis in human cerebral cortex. J. Comp. Neurol. 387, 167–178 (1997). source
• ?Could not verify

  The Materials and Methods (p. 5) say the subjects ranged from a 1-week-old newborn to 91 years; the Discussion (p. 4) addresses postnatal spine overproduction and pruning. Searches for prenatal synaptogenesis, post-conceptional weeks, and 24 PCW found no passage establishing either claimed onset at 18 or 24 weeks. (LLM, conf=0.78)

  cites [114] Petanjek, Z. et al. Extraordinary neoteny of synaptic spines in the human prefrontal cortex. Proc. Natl Acad. Sci. USA 108, 13281–13286 (2011). sourceExperimental — accuracy not yet measured

In the paper

“However, OLIG2 expression is not specific to oligodendrocyte progenitor cells and its increased expression has been shown to regulate interneuron production in organoids and chimeric mice91.”

What the sources say

• Supported

  In Results, “Human PSC-Derived OLIG2+ Ventral Forebrain NPCs Give Rise to GABAergic Neurons” (page unavailable), the paper identifies OLIG2-expressing neural progenitors that give rise to GABAergic neurons, so OLIG2 is not confined to oligodendrocyte progenitors. In Results, “Inhibiting OLIG2 Expression Rescues Overproduction of GABAergic Neurons in DS Organoids and Chimeric Mouse Brains” (page unavailable), reducing OLIG2 decreases the overproduction of specific GABAergic neuron populations in both models, supporting its role in regulating their production. (LLM, conf=0.91)

  cites [91] Xu, R. et al. OLIG2 drives abnormal neurodevelopmental phenotypes in human iPSC-based organoid and chimeric mouse models of Down syndrome. Cell Stem Cell 24, 908–926.e8 (2019). This study shows that trisomy 21 iPSCs overproduce OLIG2+ ventral forebrain neural progenitors and GABAergic neurons in organoids and in chimeric mouse brains. source

In the paper

“Similarly, when cultured for long enough to enable the generation of astrocytes, T21 iPSCs generate more of this cell type than control iPSCs, concomitant with a reduction in the generation of neurons79,82,96,103.”

What the sources say

• Supported

  The Results section, “Altered maturation of NPCs derived from DS iPSCs into neurons” (page not provided), reports reduced neuronal markers and increased astroglial markers after differentiation of trisomy 21 iPSC-derived cells compared with control cells. The Discussion also describes the generation of astroglial cells and fewer neurons from the trisomy 21 cells. (LLM, conf=0.90)

  cites [79] 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). source
• Partly supported

  The Results (Generation and differentiation of DS patient-specific hiPSCs) report that, under spontaneous differentiation, DS iPSC-derived progenitors produced more astroglia and fewer neurons than controls. The claim omits that condition: the same section reports no significant difference between DS and control lines under directed differentiation, so culturing long enough to generate astrocytes does not by itself describe the finding. (LLM, conf=0.85)

  cites [82] 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). This study identifies a role for astrocytes in regulating neuronal function in Down syndrome pathogenesis using trisomy 21 iPSC-derived neurons and astrocytes in co-cultures, drug treatment and chimeric mouse brains. sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [96] Briggs, J. A. et al. Integration-free induced pluripotent stem cells model genetic and neural developmental features of Down syndrome etiology. Stem Cell 31, 467–478 (2013). source
• Partly supported

  The Results section (‘DS-NSCs have an abnormal differentiation fate compared with NC-NSCs’; page unavailable) reports more glial progenitors and fewer neuronal progenitors in Down syndrome iPSC-derived neural stem cells than in controls. It interprets this as a shift toward glial cells, such as astrocytes, and away from neuronal cells. The study does not show that prolonged culture generated more mature astrocytes and fewer neurons. (LLM, conf=0.88)

  cites [103] Qiu, J. J., Liu, Y. N., Wei, H., Zeng, F. & Yan, J. B. Single-cell RNA sequencing of neural stem cells derived from human trisomic iPSCs reveals the abnormalities during neural differentiation of Down syndrome. Front. Mol. Neurosci. 16, 1137123 (2023). sourceExperimental — accuracy not yet measured

In the paper

“Much of the work in DS has focused on OLIG2, a chromosome 21-encoded gene that is a master regulator for oligodendrocyte development92,93,108.”

What the sources say

• ?Not checked — no full text of the sourcecites [92] Ligon, K. L., Fancy, S. P., Franklin, R. J. & Rowitch, D. H. Olig gene function in CNS development and disease. Glia 54, 1–10 (2006). source
• ?Not checked — no full text of the sourcecites [93] Rowitch, D. H., Lu, Q. R., Kessaris, N. & Richardson, W. D. An ‘oligarchy’ rules neural development. Trends Neurosci. 25, 417–422 (2002). source
• Partly supported

  The Results identify human Oligo2 on chromosome 21q. The Abstract and Discussion report that Oligo2 is expressed early in the oligodendrocyte lineage and that ectopic expression induces Sox10, but describe a causal role as suggested, not established. Calling it a “master regulator” overstates what this paper demonstrates. (LLM, conf=0.88)

  cites [108] Zhou, Q., Wang, S. & Anderson, D. J. Identification of a novel family of oligodendrocyte lineage-specific basic helix-loop-helix transcription factors. Neuron 25, 331–343 (2000). sourceExperimental — accuracy not yet measured

In the paper

“However, genetic knockdown of type I IFN receptors reduces these phenotypes148, suggesting that increased inflammatory activity in the developing brain may drive microglia to excessively prune synapses and disrupt network refinement in the developing brain.”

What the sources say

• Supported

  In Results, under “Inhibiting the expression of IFNARs rescues the defective DS microglia development” (page not specified), IFNAR1/2 shRNA lowered receptor expression in Down-syndrome iPSC-derived microglia, and the resulting chimeras showed reduced synaptic engulfment compared with controls. The Discussion identifies elevated type I IFN signaling as the mechanism targeted by IFNAR inhibition and says that inhibition corrects synaptic pruning. (LLM, conf=0.90)

  cites [148] Jin, M. et al. Type-I-interferon signaling drives microglial dysfunction and senescence in human iPSC models of Down syndrome and Alzheimer’s disease. Cell Stem Cell 29, 1135–1153.e8 (2022). source

In the paper

“Synaptic network formation, maintenance and plasticity are all closely linked to the intrinsic excitability of neurons, and the tight coordination and interdependence of these phenomena are foundational to cognitive processes such as memory and learning (reviewed in 146).”

What the sources say

• Partly supported

  The Abstract and Discussion argue that synaptic plasticity and changes in neuronal excitability work together in memory formation. The Assembly consolidation hypothesis discusses forming and stabilizing memory ensembles, but presents excitability’s contribution to consolidation as a suggestion, not an established link to synaptic-network maintenance generally. The citing sentence overstates that part of the review. (LLM, conf=0.84)

  cites [146] Lisman, J., Cooper, K., Sehgal, M. & Silva, A. J. Memory formation depends on both synapse-specific modifications of synaptic strength and cell-specific increases in excitability. Nat. Neurosci. 21, 309–314 (2018). sourceExperimental — accuracy not yet measured

In the paper

“Specifically, microglia derived from T21 iPSCs exhibit increased IFN signalling and over-prune synapses in vitro. However, genetic knockdown of type I IFN receptors reduces these phenotypes148, suggesting that increased inflammatory activity in the developing brain may drive microglia to excessively prune synapses and disrupt network refinement in the developing brain.”

What the sources say

• Supported

  The Results section on cerebral organoids reports enhanced synaptic pruning by Down-syndrome iPSC-derived microglia in an in vitro model. The IFNAR Results section reports increased type I interferon receptor expression in Down-syndrome cells and microglia, while the Discussion describes activated type I interferon responses in trisomy 21. The paper also reports that IFNAR knockdown reduces excessive pruning in microglial chimeras; that rescue experiment was not in vitro. (LLM, conf=0.88)

  cites [148] Jin, M. et al. Type-I-interferon signaling drives microglial dysfunction and senescence in human iPSC models of Down syndrome and Alzheimer’s disease. Cell Stem Cell 29, 1135–1153.e8 (2022). source

In the paper

“Co-culture with T21 iPSC-derived astrocytes also reduces the intrinsic excitability of neurons and tends to have a consequent impact on synaptic development and transmission82,135,145.”

What the sources say

• Partly supported

  The Results section, “Effects of DS astroglia on neuron synapses and ion channels” (page unavailable), reports less robust action-potential firing and no recorded synaptic activity in neurons given Down syndrome astroglial conditioned medium than in neurons given control medium. The Discussion also says that this medium fails to promote neuronal maturation and synapse formation. The experiments described used conditioned medium rather than direct co-culture, and the paper does not establish that reduced excitability caused the synaptic effects. (LLM, conf=0.85)

  cites [82] 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). This study identifies a role for astrocytes in regulating neuronal function in Down syndrome pathogenesis using trisomy 21 iPSC-derived neurons and astrocytes in co-cultures, drug treatment and chimeric mouse brains. sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section, “DS Astroglia Inhibit the Excitability of Co-cultured Neurons” (page unavailable), reports reduced evoked neuronal activity with trisomy 21 iPSC-derived astroglia. “DS Astroglia Promote Synaptic Connectivity” reports increased synapse density and mEPSC amplitude. The paper describes reduced global excitability and associated synaptic changes, but does not establish that intrinsic neuronal excitability was reduced or that its reduction caused the synaptic changes. (LLM, conf=0.85)

  cites [135] Mizuno, G. O. et al. Aberrant calcium signaling in astrocytes inhibits neuronal excitability in a human Down syndrome stem cell model. Cell Rep. 24, 355–365 (2018). sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction reports that Down syndrome astrocytes affect neuronal synaptic markers, and the discussion suggests that the observed adhesion changes may have implications for synaptogenesis. But this paper does not report that co-culture with its T21 iPSC-derived astrocytes reduces neurons’ intrinsic excitability or alters synaptic transmission. Reduced excitability appears only in the title of a different study listed in its References. (LLM, conf=0.82)

  cites [145] Ponroy Bally, B. et al. Human iPSC-derived Down syndrome astrocytes display genome-wide perturbations in gene expression, an altered adhesion profile, and increased cellular dynamics. Hum. Mol. Genet. 29, 785–802 (2020). sourceExperimental — accuracy not yet measured

In the paper

“Astrocytes isolated from DS fetal brain tissue produce less THBS1 than control astrocytes, and rodent neurons cultured with these astrocytes have fewer synapses and abnormal spine morphology than neurons cultured with control astrocytes134.”

What the sources say

• Supported

  The Methods (Cell Culture; page not provided) identify the astrocytes as originating from Down syndrome or normal human fetal brain tissue and the cocultured neurons as rat hippocampal neurons. The Results (Altered spine number and morphology; page not provided) report fewer spines and altered spine morphology with DS astrocytes than with normal astrocytes; the Discussion also reports a marked reduction in synaptic density. (LLM, conf=0.93)

  cites [134] Garcia, O., Torres, M., Helguera, P., Coskun, P. & Busciglio, J. A role for thrombospondin-1 deficits in astrocyte-mediated spine and synaptic pathology in Down’s syndrome. PLoS ONE 5, e14200 (2010). source

In the paper

“Down syndrome (DS), caused by trisomy 21 (T21), is the most common genetic cause of intellectual disability1.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [1] Quinonez, S. C. & Barsh, G. in Pathophysiology of Disease: An Introduction to Clinical Medicine (eds Hammer, G. D. & McPhee, S. J.) Ch. 2 (McGraw-Hill Education, 2019).

In the paper

“After this period of symmetric divisions, these progenitor cells — also known as radial glia — divide asymmetrically, generating postmitotic excitatory neurons that will migrate to their final location in the cerebral cortex by using the basal process of the radial glial cell as a scaffold55–58.”

What the sources say

• ?Not checked — no full text of the sourcecites [55] Rakic, P. Mode of cell migration to the superficial layers of fetal monkey neocortex. J. Comp. Neurol. 145, 61–83 (1972). source
• ?Not checked — no full text of the sourcecites [56] Noctor, S. C., Flint, A. C., Weissman, T. A., Dammerman, R. S. & Kriegstein, A. R. Neurons derived from radial glial cells establish radial units in neocortex. Nature 409, 714–720 (2001). source
• ?Not checked — no full text of the sourcecites [57] Malatesta, P., Hartfuss, E. & Gotz, M. Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage. Development 127, 5253–5263 (2000). source
• ?Not checked — no full text of the sourcecites [58] Doetsch, F., Caille, I., Lim, D. A., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 703–716 (1999). source

In the paper

“However, neurons derived from fetal DS NPCs are more sensitive to reactive oxygen species96 than those of controls, which may indicate a vulnerability to cell death.”

What the sources say

• ?Not checked — no full text of the sourcecites [96] Briggs, J. A. et al. Integration-free induced pluripotent stem cells model genetic and neural developmental features of Down syndrome etiology. Stem Cell 31, 467–478 (2013). source

In the paper

“Before neurogenesis starts, progenitor cells located in the ventricular zone divide symmetrically, thus amplifying the pool of progenitor cells that will generate the neurons and macroglia (astrocytes and oligodendrocytes) that compose the cerebral cortex52–54.”

What the sources say

• ?Not checked — no full text of the sourcecites [52] Gotz, M. & Huttner, W. B. The cell biology of neurogenesis. Nat. Rev. Mol. Cell Biol. 6, 777–788 (2005). source
• ?Not checked — no full text of the sourcecites [53] McConnell, S. K. Constructing the cerebral cortex: neurogenesis and fate determination. Neuron 15, 761–768 (1995). source
• ?Not checked — no full text of the sourcecites [54] Rakic, P. A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution. Trends Neurosci. 18, 383–388 (1995). source

In the paper

“Analysis of post-mortem brains over the past 100 years has consistently revealed that there are fewer cells in the brains of individuals with DS and that this underlies the reduced brain volume associated with the disorder (Fig. 1).”

In the paper

“Some areas of the cortex, especially those in the temporal and frontal lobes, exhibit up to 50% fewer cells in individuals with DS than in healthy individuals, whereas other areas, such as the parietal lobe, are largely preserved7.”

What the sources say

• ?Not checked — no full text of the sourcecites [7] Pinter, J. D., Eliez, S., Schmitt, J. E., Capone, G. T. & Reiss, A. L. Neuroanatomy of Down’s syndrome: a high-resolution MRI study. Am. J. Psychiatry 158, 1659–1665 (2001). This high-resolution MRI study confirms that volumetric brain differences occur at early ages in Down syndrome. source

In the paper

“Reduced neurogenesis can be caused by slower proliferation of progenitors that limits their expansion and/or by the premature exit of progenitors from the cell cycle (differentiation), both of which will reduce the number of symmetric divisions and, thus, deplete the pool of remaining progenitors needed to make new neurons (Fig. 2).”

In the paper

“Furthermore, GFAP is problematic as an astrocyte marker because it is not abundantly expressed in all astrocytes and is also expressed by radial glia during early development100.”

What the sources say

• ?Not checked — no full text of the sourcecites [100] Choi, B. H. Glial fibrillary acidic protein in radial glia of early human fetal cerebrum: a light and electron microscopic immunoperoxidase study. J. Neuropathol. Exp. Neurol. 45, 408–418 (1986). source

In the paper

“The generation of the six-layer cortical plate occurs in an inside-out fashion, with the early-born neurons establishing layer 6, then layer 5, and so forth59.”

What the sources say

• ?Not checked — no full text of the sourcecites [59] Rakic, P. Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition. Science 183, 425–427 (1974). source

In the paper

“The fact that this reduction in neuron number appears at and before birth supports the idea that the generation of neurons is reduced during the prenatal period in DS and establishes impaired neurogenesis as a key feature of DS49,50 (Fig. 2).”

What the sources say

• ?Not checked — no full text of the sourcecites [49] Lott, I. T. & Dierssen, M. Cognitive deficits and associated neurological complications in individuals with Down’s syndrome. Lancet Neurol. 9, 623–633 (2010). source
• ?Not checked — no full text of the sourcecites [50] Stagni, F., Giacomini, A., Emili, M., Guidi, S. & Bartesaghi, R. Neurogenesis impairment: an early developmental defect in Down syndrome. Free Radic. Biol. Med. 114, 15–32 (2018). source

In the paper

“Therefore, although the imbalance in excitatory and inhibitory synaptic transmission observed in mouse models of DS is not borne out in iPSC models of T21, a reduced capacity for synaptic plasticity as a whole does manifest in these paradigms.”

In the paper

“Specifically, detection of reduced synaptic proteins and neurotransmitters implicates alterations to synapse development in DS, but whether these reductions reflect reduced synapse number or alterations to individual synapses cannot be determined without higher resolution.”

In the paper

“In vitro data from human iPSC-derived neurons indicate that neurons from humans with DS not only have reduced excitatory synaptic density relative to controls but also exhibit functional deficits in excitatory synaptic transmission, including reduced frequency of spontaneous post-synaptic currents81,131.”

What the sources say

• ?Not checked — no full text of the sourcecites [81] Weick, J. P. et al. Deficits in human trisomy 21 iPSCs and neurons. Proc. Natl Acad. Sci. USA 110, 9962–9967 (2013). source
• ?Not checked — no full text of the sourcecites [131] Araujo, B. H. S. et al. Down syndrome iPSC-derived astrocytes impair neuronal synaptogenesis and the mTOR pathway in vitro. Mol. Neurobiol. 55, 5962–5975 (2018). source

In the paper

“In fact, the sole electron microscopic study of the fetal brain of individuals with DS119 reports that the synapse density of cortical neurons is comparable in individuals with DS and controls at midfetal stages, but that measures of synaptic morphology — such as the width and length of the post-synaptic density — are reduced during late fetal development (Fig. 3b).”

What the sources say

• ?Not checked — no full text of the sourcecites [119] Petit, T. L., LeBoutillier, J. C., Alfano, D. P. & Becker, L. E. Synaptic development in the human fetus: a morphometric analysis of normal and Down’s syndrome neocortex. Exp. Neurol. 83, 13–23 (1983). Through electron microscopy of neonatal DS and control brains, this study reveals a higher percentage of primitive synaptic contacts in the DS tissue. source

In the paper

“However, a definitive investigation of how non-neuronal cells impact the inhibition–excitation ratio has not yet been undertaken.”

In the paper

“Additionally, the levels of synaptic proteins (such as synaptosomal-associated protein 25 (SNAP25) and alpha-soluble NSF attachment protein (SNAPA)), neurotransmitters (particularly GABA, dopamine and serotonin), and neurotransmitter receptors are reduced in fetal brains of individuals with DS relative to controls120–122.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [120] Weitzdoerfer, R., Dierssen, M., Fountoulakis, M. & Lubec, G. Fetal life in Down syndrome starts with normal neuronal density but impaired dendritic spines and synaptosomal structure. J. Neural Transm. Suppl. 2001, 59–70 (2001).
• ?Not checked — no full text of the sourcecites [121] Whittle, N., Sartori, S. B., Dierssen, M., Lubec, G. & Singewald, N. Fetal Down syndrome brains exhibit aberrant levels of neurotransmitters critical for normal brain development. Pediatrics 120, e1465–e1471 (2007). source
• ?Not checked — no full text of the sourcecites [122] Falsafi, S. K., Dierssen, M., Ghafari, M., Pollak, A. & Lubec, G. Reduced cortical neurotransmitter receptor complex levels in fetal Down syndrome brain. Amino Acids 48, 103–116 (2016). source

In the paper

“Such findings support the suggestion that synaptic deficits are present at early developmental stages in DS, but the limited resolution of the techniques used in some of these investigations preclude the drawing of specific conclusions.”

What the sources say

• ?Not checked — no full text of the sourcecites [119] Petit, T. L., LeBoutillier, J. C., Alfano, D. P. & Becker, L. E. Synaptic development in the human fetus: a morphometric analysis of normal and Down’s syndrome neocortex. Exp. Neurol. 83, 13–23 (1983). Through electron microscopy of neonatal DS and control brains, this study reveals a higher percentage of primitive synaptic contacts in the DS tissue. source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [120] Weitzdoerfer, R., Dierssen, M., Fountoulakis, M. & Lubec, G. Fetal life in Down syndrome starts with normal neuronal density but impaired dendritic spines and synaptosomal structure. J. Neural Transm. Suppl. 2001, 59–70 (2001).
• ?Not checked — no full text of the sourcecites [121] Whittle, N., Sartori, S. B., Dierssen, M., Lubec, G. & Singewald, N. Fetal Down syndrome brains exhibit aberrant levels of neurotransmitters critical for normal brain development. Pediatrics 120, e1465–e1471 (2007). source
• ?Not checked — no full text of the sourcecites [122] Falsafi, S. K., Dierssen, M., Ghafari, M., Pollak, A. & Lubec, G. Reduced cortical neurotransmitter receptor complex levels in fetal Down syndrome brain. Amino Acids 48, 103–116 (2016). source

In the paper

“This ultimately results in an overabundance of synapses in the infant brain, but many of these connections are eliminated via robust synaptic pruning that occurs from early childhood through adolescence112.”

What the sources say

• ?Not checked — no full text of the sourcecites [112] Huttenlocher, P. R. Synaptic density in human frontal cortex — developmental changes and effects of aging. Brain Res. 163, 195–205 (1979). source

In the paper

“Neurons in the fetal brain of individuals with DS do not show such differences in spine number or morphology (Fig. 3a).”

In the paper

“It is important to note that information from Golgi and electron microscopy studies to date have been limited to the motor and visual cortices, whereas RNA and protein analyses have incorporated the entire fetal cortex.”

In the paper

“The earliest reports using Golgi staining of human brain tissue provided consistent evidence that newborns and infants with DS have substantial deficits in spine density and abnormal spine morphology115–118.”

What the sources say

• ?Not checked — no full text of the sourcecites [115] Marin-Padilla, M. Structural abnormalities of the cerebral cortex in human chromosomal aberrations: a Golgi study. Brain Res. 44, 625–629 (1972). source
• ?Not checked — no full text of the sourcecites [116] Marin-Padilla, M. Pyramidal cell abnormalities in the motor cortex of a child with Down’s syndrome. A Golgi study. J. Comp. Neurol. 167, 63–81 (1976). source
• ?Not checked — no full text of the sourcecites [117] 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 (1985). This Golgi analysis of DS fetal and infant brains shows the same neuronal morphology and spine counts as those of control fetuses; however, DS brains had shorter basilar dendrites and decreased numbers of spines with altered morphology and defective cortical layering. source
• ?Not checked — no full text of the sourcecites [118] Takashima, S., Iida, K., Mito, T. & Arima, M. Dendritic and histochemical development and ageing in patients with Down’s syndrome. J. Intellect. Disabil. Res. 38, 265–273 (1994). source

In the paper

“however, DS brains had shorter basilar dendrites and decreased numbers of spines with altered morphology and defective cortical layering”

What the sources say

• ?Not checked — no full text of the sourcecites [117] 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 (1985). This Golgi analysis of DS fetal and infant brains shows the same neuronal morphology and spine counts as those of control fetuses; however, DS brains had shorter basilar dendrites and decreased numbers of spines with altered morphology and defective cortical layering. source

In the paper

“Human pluripotent stem cells enable modelling of human neural development, albeit with some limitations, including reduced complexity and the immaturity of the cell types generated (Box 1).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Box 1

In the paper

“T21 microglia have also been implicated in altered synaptic development, further suggesting that non-neuronal cell types may have a major role in disrupted synapse development in DS.”

In the paper

“In addition, we are learning more about the non-coding regions of the genome, and it is becoming clear that the impact of the numerous non-coding RNAs encoded on HSA21 is probably key to understanding many cellular processes.”

In the paper

“This Golgi analysis of DS fetal and infant brains shows the same neuronal morphology and spine counts as those of control fetuses”

What the sources say

• ?Not checked — no full text of the sourcecites [117] 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 (1985). This Golgi analysis of DS fetal and infant brains shows the same neuronal morphology and spine counts as those of control fetuses; however, DS brains had shorter basilar dendrites and decreased numbers of spines with altered morphology and defective cortical layering. source