Advertisement

Development and Aging in Down’s Syndrome

  • K. E. Wisniewski
  • M. Dambska

Abstract

The delayed development and impaired maturation of the central nervous system (CNS) in Down’s syndrome (DS) is presented from the prenatal period until premature aging. The parameters examined by many authors, such as head measurements, brain weight and shape, and light and electron microscopic examination of selected cortical areas are discussed. The data suggest that the first differences between DS and non-DS brains appear during the second half of fetal life when several minor abnormalities in the number of cortical neurons and synaptic structure are seen. Postnatal development in DS looks evidently disturbed and retarded. The decreased neuronal density, reduced number of synapses, and abnormal features of these synapses are most accentuated during and after midinfancy. The distribution of neuronal changes reveals a particular deficit of granular neurons, leading to a deep reorganization of cortical structure. The heterogeneity of anomalies occurring during brain development that never reach a normal level overlap with the process of aging, which occurs in the third decade of life and even before this age. Neuropathological changes of the Alzheimer type, such as fibrillary tangles and senile plaques, develop 20 to 30 years earlier in the DS than the non-DS population, and in DS dementia occurs later than morphological features of aging. We hope that the review of the complex events occurring during delayed and even more abnormal development in DS cases overlapping with premature aging will be useful for further genetic study of the pathomechanism of this syndrome.

Keywords

Down Syndrome Senile Plaque Premature Aging Brain Weight Neuronal Density 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Apert E (1914): Mongolism. Le monde médicale 24:201Google Scholar
  2. Becker LE, Armstrong DL, Chan F (1986): Dendritic atrophy in children with Down’s syndrome. Ann Neurol 20:520–526CrossRefGoogle Scholar
  3. Benda CE (1969): Down’s Anomaly, 2nd Edition, New York: Grume StrattonGoogle Scholar
  4. Benda CE (1971): Mongolism. In: Pathology of the Nervous System, Vol. 2. Mencken J, ed. McGraw-Hill Inc., pp. 1361–1371Google Scholar
  5. Bertrand T, Koffas D (1946): Cas D’ idiotie mongolienne adulte avec nombreuses plaques senileg et concretions calcarine pallidales. Rev Neurol 78:338–345Google Scholar
  6. Brooksbank BWL, Walker D, Balazs R, Jorgensen OS (1989): Neuronal maturation in the fetal brain in Down’s syndrome. Early Hum Dev 18:237–246CrossRefGoogle Scholar
  7. Courchesne E (1988): Physioanatomical considerations in Down’s syndrome. In: The Psychobiology of Down Syndrome, Nadel L, ed. Cambridge, MA: MIT Press, pp. 291–313Google Scholar
  8. Crome L, Covie V, Slatter E (1966): A statistical note on cerebellar and brain stem weight in mongolism. J Ment Defic Res 10:69–72Google Scholar
  9. Crome L, Stern J (1972): Pathology of Mental Retardation. Baltimore: William and WilkinsGoogle Scholar
  10. Cronk CE (1978): Growth of children with Down syndrome: birth to age 3. Pediatrics 61:564–568Google Scholar
  11. Cronk E, Pueschel S (1983): Autopometric studies. In: A Study of the Young Child with Down Syndrome. Pueschel SSM, ed). New York: Hum Sci Press, pp. 105–141Google Scholar
  12. Dalton AJ, Wisniewski HM (1990): Down’s syndrome and the dementia of Alzheimer’s disease. Int Rev Psychiatr 2:41–50CrossRefGoogle Scholar
  13. Davidoff ML (1928): The brain in mongolian idiocy. Arch Neurol Psvchiatr 20:1229–1257Google Scholar
  14. Evenhuis HM (1990): The natural history of dementia in Down’s syndrome. Arch Neurol 47:237–263CrossRefGoogle Scholar
  15. Ferrer J, Gulotta F (1990): Down’s syndrome and Alzheimer’s disease: dendritic spines in the hippocampus. Acta Neuropath 79:680–685CrossRefGoogle Scholar
  16. Friede RL (1989): Developmental Neuropathology. Berlin: Springer-VerlagCrossRefGoogle Scholar
  17. Gans A (1925): Anatomische Beobachtungen bei der mongoloiden Idiotie. Nederl Tijdschr Geneesk 69:922–925Google Scholar
  18. Godridge H, Reymonds GP, Czudek C, et al. (1987): Alzheimer-like neurotransmitter deficit in adult Down’s syndrome brain tissue. J Neurol Neurosurg Psychriatr 50:775–778CrossRefGoogle Scholar
  19. Gulotta F, Rehder H (1974): Chromosomal anomalies and central nervous system. Birth Pathol 152:74–80Google Scholar
  20. Haberland C (1969): Alzheimer’s disease in Down’s syndrome: clinical-neuro-pathological observations. Acta Neurol Bela 69:369–380Google Scholar
  21. Huttenlocher PR (1984): Synapse elimination and plasticity in developing human cerebral cortex. Am Ment Def 88:488–496Google Scholar
  22. Jacob H (1956): Mongolism. In: Hanbuch der speziellen pathologischen Anat. u. Histologie. Vierter Teil, Lubarsch O, Henke F, Rossle E, eds. Berlin: Springer-Verlag, pp. 82–98Google Scholar
  23. Jervis GA (1948): Early senile dementia in mongoloid idiocy. J Psychiatr 145: 102–106Google Scholar
  24. Kemper TL (1988): Neuropathology of Down syndrome. In: The Psychobiology of Down’s Syndrome. Nadel L, ed. Cambridge, MA: The MIT Press, pp. 269–289Google Scholar
  25. Khachatur-Iants LS (1985): Diagnosis of Alzheimer disease. Ann Neurol 42:1097–1105CrossRefGoogle Scholar
  26. Lai F, Williams R (1989): Alzheimer’s dementia in Down’s syndrome. Arch Neurol 46:849–853CrossRefGoogle Scholar
  27. Lott JT (1986): The neurology of Down syndrome. In: The Neurobiology of Down Syndrome. Epstein CJ, ed. New York: Raven Press, pp. 17–25Google Scholar
  28. McGrother CW, Marshall B (1990): Recent trends in incidence, morbidity and survival in Down’s syndrome. J Neurol Def Research 34:49–57Google Scholar
  29. Optiz JM, Gilbert-Barnes EF (1990): Reflections on the pathogenesis of Down syndrome. Am Med Genet (in press).Google Scholar
  30. Petit TL, LeBoutillier JC, Alfano DP, Becker LE (1984): Synaptic development in the human fetus. A morphometric analysis of normal and Down’s syndrome neocortex. Exp Neurol 83:13–23CrossRefGoogle Scholar
  31. Pierotti AR, Harmor AJ, Simpson J, et al. (1986): High-molecular-weight forms of somatostatin are reduced in Alzheimer’s disease and Down’s syndrome. Neurosci Lett 63:141–146CrossRefGoogle Scholar
  32. Rabe A, Wisniewski KE, Schupf N, Wisniewski HM (1990): Relationship of Down’s syndrome to Alzheimer’s disease. In: Application of Basic Neuroscience to Child Psychiatry, Deutsch S, Weizman A, eds. R. Weizman Plum Publ Corp, pp. 325–340Google Scholar
  33. Roche AF (1966): The cranium in mongolism. Acta Neurol Scand 42:62–78CrossRefGoogle Scholar
  34. Ross MH, Galaburda AM, Kemper TL (1984): Down’s syndrome: Is there a decreased population of neurons? Neurology 34:909–916Google Scholar
  35. Scott BS, Petit TL, Becker LE, Edwards BAV (1982): Abnormal electric membrane properties of Down’s syndrome DRG neurons in cell culture. Dev Brain Res 2:257–270CrossRefGoogle Scholar
  36. Scott BS, Beeker LE, Petit TL (1983): Neurobiology of Down’s syndrome. Progress in Neurobiology 21:199–237CrossRefGoogle Scholar
  37. Schmidt-Sidor B, Wisniewski KE, Shepard TH, Sersen EA (1990): Brain growth in Down syndrome subjects 15 to 22 weeks of gestational age and birth to 60 months. Clin Neuropath (in press).Google Scholar
  38. Shapiro MB, Luxemburg JS, Kaye JA, Haxby JV, Friedland RP, Rapaport SJ (1989): Serial quantitative CT analysis of brain morphometrics in adult Down’s syndrome of different ages. Neurology 39:1349–1353Google Scholar
  39. Shortridge BA, Vogel FS, Burger PC (1985): Topographic relationship between neurofibrillary change and acetylocholinesterase-rich neurons in the upper brain stem of patients with senile dementia of the Alzheimer’s type and Down’s syndrome. Clin Neuropath 4:227–237Google Scholar
  40. Solitare JB (1990): Aging and brain weight in Down’s syndrome. Neurology 40:729Google Scholar
  41. Suetsugu H, Mehraein P (1980): Spine distribution along the apical dendrites of the pyramidal neurons in Down’s syndrome. Acta Neuropathol 50:207–210CrossRefGoogle Scholar
  42. Sylvester PE (1983): The hippocampus in Down’s syndrome. J Ment Defic Res 27:227–236Google Scholar
  43. Takashima S, Becker LE, Armstrong DL, Chan F (1981): 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 225:1–21CrossRefGoogle Scholar
  44. Takashima S, Jeshima A, Nakamura H, Becker LE (1989): Dendrites, dementia and Down syndrome. Brain Dev 11:131–133CrossRefGoogle Scholar
  45. Thase ME (1988): The relationship between Down’s syndrome and Alzheimer’s disease. In: The Psychobiology of Down Syndrome. Nadel L, ed. Cambridge, MA: The MIT Press, pp. 345–368Google Scholar
  46. Wisniewski KE, French JH, Rosen JF, Kozlowski PB, Tenner M, Wisniewski HM (1982): Basal ganglia calcification (BGC) in Down’s syndrome (DS)— Another manifestation of premature aging. Ann NY Acad Sci 396:179–189CrossRefGoogle Scholar
  47. Wisniewski HM, Merz GS (1984): Aging, Alzheimer’s disease and developmental disabilities. In: Aging and Developmental Disabilities. Janieki MP, Wisniewski HM, eds. Baltimore: Brookes, pp. 177–184Google Scholar
  48. Wisniewski HM, Rabe A (1986): Discrepancy between Alzheimer type neuropathology and dementia in persons with Down’s syndrome. Ann NY Acad Sci 447:247–259CrossRefGoogle Scholar
  49. Wisniewski KE, Laure-Kamionowska M, Wisniewski HM (1984): Evidence of arrest of neurogenesis and synaptogenesis in brains of patients with Down’s syndrome. N Engl J Med 18:1187–1188Google Scholar
  50. Wisniewski KE, Dalton AJ, McLachlan C, Wen GY, Wisniewski HM (1985a): Alzheimer’s disease in Down’s syndrome. Neurology 35:957–961Google Scholar
  51. Wisniewski KE, Wisniewski HM, Wen GY (1985b): Occurrence of neuropatho-logical changes and dementia of Alzheimer’s disease in Down’s syndrome. Ann Neurol 17:278–282CrossRefGoogle Scholar
  52. Wisniewski KE, Laure-Kamionowska M, Connell F, Wen GY (1986): Neuronal density and synaptogenesis in the postnatal stage of brain maturation in Down syndrome. In: Neurobiology in Down Syndrome, Epstein CJ, ed. New York: Raven Press, pp. 29–44Google Scholar
  53. Wisniewski KE, Schmidt-Sidor B (1989): Postnatal delay of myelin formation in brains from Down syndrome infants and children. Clinical Neuropathology 2:55–62Google Scholar
  54. Wisniewski KE (1990): Down syndrome children often have brain with maturation delay, retardation of growth and cortical dysgenesis. Am J Med Genet 7:274–281Google Scholar
  55. Yates CML, Simpson J, Maloney AFY, et al. (1980): Alzheimer-like cholinergic deficiency in Down’s syndrome. Lancet 11:979CrossRefGoogle Scholar
  56. Yates CM, Simpson J, Gordon A, et al. (1983): Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and Down’s syndrome. Brain Res 280:119–126CrossRefGoogle Scholar
  57. Zellweger H (1977): Down syndrome. In: Handbook of Clinical Neurology. Vinken P, Bruyn GW, eds. Vol. 31 Pt II, Amsterdam, NY; Oxford: North Holland Publ Co., pp. 367–469Google Scholar

Copyright information

© Birkhäuser Boston 1992

Authors and Affiliations

  • K. E. Wisniewski
  • M. Dambska

There are no affiliations available

Personalised recommendations