Total numbers of neurons and glial cells in cortex and basal ganglia of aged brains with Down syndrome-a stereological study.
Abstract
The total numbers of neurons and glial cells in the neocortex and basal ganglia in adults with Down syndrome (DS) were estimated with design-based stereological methods, providing quantitative data on brains affected by delayed development and accelerated aging. Cell numbers, volume of regions, and densities of neurons and glial cell subtypes were estimated in brains from 4 female DS subjects (mean age 66 years) and 6 female controls (mean age 70 years). The DS subjects were estimated to have about 40% fewer neocortical neurons in total (11.1 × 10(9) vs. 17.8 × 10(9), 2p ≤ 0.001) and almost 30% fewer neocortical glial cells with no overlap to controls (12.8 × 10(9) vs. 18.2 × 10(9), 2p = 0.004). In contrast, the total number of neurons in the basal ganglia was the same in the 2 groups, whereas the number of oligodendrocytes in the basal ganglia was reduced by almost 50% in DS (405 × 10(6) vs. 816 × 10(6), 2p = 0.01). We conclude that trisomy 21 affects cortical structures more than central gray matter emphasizing the differential impairment of brain development. Despite concomitant Alzheimer-like pathology, the neurodegenerative outcome in a DS brain deviates from common Alzheimer disease.
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The average number of glial cells in the human brain is estimated to be 84.61 ± 9.83 × 10^9, with the population of glial cells in the neocortex estimated at from 18.2 to 38.6 × 10^9.
“The average number of glial cells in the human brain is estimated to be 84.61 ± 9.83 × 109 (Herculano-Houzel, 2009), with the population of glial cells in the neocortex estimated at from 18.2 to 38.6 × 109”
From Human Brain/Cloud Interface (2019) · cites this paper as Karlsen and Pakkenberg, 2011
The Results (page unavailable) estimate 18.2 × 10^9 neocortical glial cells in the control group, supporting the lower figure. They do not give 38.6 × 10^9 or an 18.2–38.6 × 10^9 range; the reported range for controls is 15.0–21.8 × 10^9. The whole-brain estimate is explicitly attributed to Herculano-Houzel (2009) in the citing sentence, not to this paper. (LLM, conf=0.87)
Experimental — accuracy not yet measuredPost-mortem studies show reduced myelin content and fewer oligodendrocytes in DS striatum.
“This is in agreement both with previous studies showing that DS children manifest learning and memory problems in late infancy which often worsen in adolescence (Koo et al., 1992; Lanfranchi et al., 2010) and with post-mortem studies that show reduced myelin content (Abraham et al., 2012; Wisniewski, 1990; Wisniewski and Schmidt-Sidor, 1989) and fewer oligodendrocytes in DS striatum (Karlsen and P”
From Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination (2016) · cites this paper as Karlsen and Pakkenberg, 2011
The Basal Ganglia results report significantly fewer oligodendrocytes in post-mortem brains from older adults with Down syndrome than in controls. The counts are for the basal ganglia as a whole, which include the striatum; the paper does not report a separate striatal count. Reduced myelin content is attributed to other citations in the citing sentence, not to this source. (LLM, conf=0.86)
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Cites
The efficiency of systematic sampling in stereology—reconsidered
GUNDERSEN, H. J. G., JENSEN, E. B. V., KIÊU, K., & NIELSEN, J. (1999) · Journal of Microscopy · doi:10.1046/j.1365-2818.1999.00457.x · Cited by 1,317 · see citing works
Neuroanatomy of Down’s Syndrome: A High-Resolution MRI Study
Pinter, J. D., Eliez, S., Schmitt, J. E., Capone, G. T., & Reiss, A. L. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.10.1659 · Cited by 452 · see citing works
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Reduced cell number in the neocortical part of the human fetal brain in Down syndrome
Larsen, K. B., Laursen, H., Græm, N., Samuelsen, G. B., Bogdanovic, N., & Pakkenberg, B. (2008) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2008.05.007 · Cited by 87 · cited 3× · see citing works
“…in the adult neocortex of DS is permanent, it is likely the consequence of uncompensated developmental deficits evident as early as the 19th gestational week at which time there are 34% fewer neocortical cells in the forebrain as compared with normal brains as reported by Larsen et al. (2008).”
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Research works printed but not linked: 2
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von Bartheld, C. S., Bahney, J., & Herculano‐Houzel, S. (2016) · Journal of Comparative Neurology · doi:10.1002/cne.24040 · Cited by 1,063 · see citing works
Olmos-Serrano, J. L., Kang, H. J., Tyler, W. A., Silbereis, J. C., Cheng, F., Zhu, Y., Pletikos, M., Jankovic-Rapan, L., Cramer, N. P., Galdzicki, Z., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.042 · Cited by 239 · see citing works
“…which often worsen in adolescence (Koo et al., 1992; Lanfranchi et al., 2010), and with postmortem studies that show reduced myelin content (Ábrahám et al., 2012; Wisniewski, 1990; Wisniewski and Schmidt-Sidor, 1989) and fewer oligodendrocytes in DS striatum (Karlsen and Pakkenberg, 2011).”
Architecture of the cerebral cortical association connectome underlying cognition
Bota, M., Sporns, O., & Swanson, L. W. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1504394112 · Cited by 231 · see citing works
Martins, N. R. B., Angelica, A., Chakravarthy, K., Svidinenko, Y., Boehm, F. J., Opris, I., Lebedev, M. A., Swan, M., Garan, S. A., Rosenfeld, J. V., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00112 · Cited by 91 · see citing works
Salvesen, L., Ullerup, B. H., Sunay, F. B., Brudek, T., Løkkegaard, A., Agander, T. K., Winge, K., & Pakkenberg, B. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.11.008 · Cited by 85 · see citing works
Self-citationSynaptophysin and Synaptojanin-1 in Down Syndrome are Differentially Affected by Alzheimer's Disease
Martin, S. B., Dowling, A. L. S., Lianekhammy, J., Lott, I. T., Doran, E., Murphy, M. P., Beckett, T. L., Schmitt, F. A., & Head, E. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-140795 · Cited by 64 · see citing works
Changes in the cell population in brain white matter in multiple system atrophy
Nykjær, C. H., Brudek, T., Salvesen, L., & Pakkenberg, B. (2017) · Movement Disorders · doi:10.1002/mds.26979 · Cited by 51 · see citing works
Self-citation
- Authors
- Karlsen, A. S., & Pakkenberg, B.
- Affiliations
- Bispebjerg Hospital (DK)
- ORCID
- Pakkenberg, B.
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-03-22
- Volume
- 21
- Issue
- 11
- Pages
- 2519-2524
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2119704718
- Cited by
- 75
- References
- 4
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 9 · 2020: 2 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 5 · 2015: 5 · 2014: 6 · 2013: 4 · 2012: 7
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Topics
- 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
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Down syndrome, neocortical neurons, glial cells, basal ganglia, oligodendrocytes, brain aging, accelerated brain aging, neurodegeneration, brain development, stereology
- MeSH terms
- Aged, Aging, Basal Ganglia, Cell Count, Cerebral Cortex, Down Syndrome, Female, Humans, Middle Aged, Neuroglia, Neurons
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