Research Article
Volume 14 Issue 1 - 2022
Microglia and Astrocytes in Postmortem Human Brain Increase in Parallel with Aging
Anne K Vehmas*
Department of Pathology, Neuropathology Division, The Johns Hopkins University, School of Medicine, USA
*Corresponding Author: Anne K Vehmas, Department of Pathology, Neuropathology Division, The Johns Hopkins University, School of Medicine, USA.
Received: November 12, 2021; Published: December 30, 2021


We showed previously significantly increased fractional areas (FA) of HLA- DR and GFAP immunoreactivities (microglia and astrocytes) in brains of patients with Alzheimer´s disease (AD). This prompted us to assess FA and qualitative alterations in HLA-DR, GFAP, amyloid-β-peptide (Aβ) and phospho-tau immunoreactivities during aging in human neocortex of 11 young (mean 26 years), 9 middle aged (mean 48 years) and 11 elderly (mean 82 years) healthy persons.

The mean FAs of HLA-DR and GFAP were similar in young and middle-aged persons, but significantly greater (p < 0.05 resp. <0.004) in young vs. elderly persons. In middle-aged vs. elderly persons only the increase in FA-GFAP reached significance (p < 0.001). while that in FA-HLA-DR did not. In the young microglia were located predominantly perivascularly, in the elderly widely in the neuropil. Aβ immunoreactivity did not appear until in middle- aged persons, tau-staining remained negative throughout.

In conclusion: Brain cells of innate immunity, microglia and astrocytes, increase during aging probably reflecting cumulative immunologically challenging events, including those of AD, possibly also compensating for their senescence and fading protective capacity.

Keywords: Microglia; Astrocytes; Inflammation; Aging; Senescence; Amyloid; β-peptide; Tau; Quantification


  1. Allen NJ and Barres BA. “Glia - more than just brain glue”. Nature 457 (2009): 675-677.
  2. Banati RB., et al. “Cytotoxicity of microglia”. Glia 7 (1993): 111-118.
  3. Bitto, A., et al. “Stress-induced senescence in human and rodent astrocytes”. Experimental Cell Research 316 (2010): 2961-2968.
  4. Chesler M. “The regulation and modulation of pH in the nervous system”. Progress in Neurobiology 34 (1990): 401-427.
  5. Ferrer I., et al. “Neuropathology and pathogenesis of encephalitis following amyloid- beta immunization in Alzheimer’s disease”. Brain Pathology 14 (2004): 11-20.
  6. Fiala M., et al. “Phagocytosis of amyloid-beta and inflammation: two faces of innate immunity in Alzheimer’s disease”. Journal of Alzheimer's Disease 11 (2007): 457-463.
  7. Funato H., et al. “Quantitation of amyloid protein (Aβ in the cortex during aging and in Alzheimer’s disease)”. American Journal of Pathology 152 (1998): 1633-1640.
  8. Geula C., et al. “Aging renders the brain vulnerable to amyloid - protein neurotoxicity”. Nature Medicine 7 (1998): 827-831.
  9. , et al. “Specific domains of beta- amyloid from Alzheimer plaque elicit neuron killing in human microglia”. Journal of Neuroscience 16 (1996): 6021-6037.
  10. Graeber MB and Streit WJ. “Microglia: biology and pathology”. Acta Neuropathologica 19 (2010): 89-105.
  11. Hickey WF and Kimura H. “Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo”. Science 239 (1988): 290-292.
  12. Holmin S., et al. “Intracerebral inflammation after human brain contusion”. Neurosurgery 42 (1998): 291-298.
  13. Husemann, J., et al. “Scavenger receptors in neurobiology and neuropathology: their role on microglia and other cells of the nervous system”. Glia 40 (2002): 195-205.
  14. Klegeris A and McGeer PL. “Amyloid protein enhances macrophage production of oxygen free radicals and glutamate”. Journal of Neuroscience 49 (1997): 229- 235.
  15. Kok, E.H., et al. “Apolipoprotein E-Dependent Accumulation of Alzheimer Disease-Related Lesions Begins in Middle Age”. Annals of Neurology 65 (2009): 650-657.
  16. Malm T et al. “The role and therapeutic potential of monocytic cells in Alzheimer's disease”. Glia 58 (2010): 889-900.
  17. McGeer PL and McGeer, E.G. “Inflammation, autotoxicity and Alzheimer disease”. Neurobiology of Aging 22 (2001): 799-809.
  18. Miller KR and Streit WJ. “The effect of aging, injury and disease on microglial function: a case for cellular senescence”. Neuron Glia Biology 3 (2007): 245-253.
  19. Neumann H., et al. “Debris clearance by microglia: an essential link between degeneration and regeneration”. Brain 132 (2009): 288-295.
  20. Nicoll JA., et al. “Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report”. Nature Medicine 9 (2003): 448-452.
  21. Nicoll JA., et al. “Abeta species removal after abeta42 immunization”. Journal of Neuropathology & Experimental Neurology 65 (2006): 1040-1048.
  22. Ogura K., et al. “Effects of ageing on microglia in the normal rat brain: Immunohistochemical observations”. NeuroReport 5 (1994): 1224-1226.
  23. Ransohoff RM and Cardona AE. “The myeloid cells of the central nervous system parenchyma”. Nature7321 (2010): 253-262.
  24. Roubenoff R., et al. “Monocyte cytokine production in an elderly population: effect of age and inflammation”. The Journals of Gerontology Series A Biological Sciences and Medical Sciences1 (1998): M20-26.
  25. Schwab C and McGeer PL. “Inflammatory aspects of Alzheimer disease and other neurodegenerative disorders”. Journal of Alzheimer's Disease 13 (2008): 359-369.
  26. Schwartz M and Schechter R. “Systemic inflammatory cells fight off neurodegenerative disease”. Nature Reviews Neurology 6 (2010): 405-410.
  27. Snowdon DA. “Aging and Alzheimer's disease: lessons from the Nun Study”. Gerontologist 37 (1997): 150-156.
  28. Sofroniew MV. “Molecular dissection of reactive astrogliosis and glial scar formation”. Trends in Neurosciences12 (2009): 638-647.
  29. Sofroniew MV and Vinters H. “Astrocytes: biology and pathology”. Acta Neuropathologica 119 (2010): 7-1135.
  30. Streit WJ., et al. “Functional plasticity of microglia: a review”. Glia 1 (1988): 301-307.
  31. Streit WJ., “Microglia as neuroprotective, immunocompetent cells of the CNS”. Glia 40 (2002): 133-139.
  32. Streit WJ., et al. “Dystrophic microglia in the aging human brain”. Glia 45 (2004): 208-212.
  33. Streit WJ and Xue QS. “Life and death of microglia”. Journal of Neuroimmune Pharmacology 4 (2009): 371-379.
  34. Streit W., et al. “Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer’s disease”. Acta Neuropathologica 118 (2009): 475-485.
  35. Theele DP and Streit, WJ. “A chronicle of microglial ontogeny”. Glia 7 (1993): 5- 8.
  36. Vehmas AK., et al. “Immune reactive cells in senile plaques and cognitive decline in Alzheimer’s disease”. Neurobiology of Aging 24 (2003): 321-331.
  37. von Bernhardi R., et al. “Aging-dependent changes of microglial cells and their relevance for neurodegenerative disorders”. Journal of Neurochemistry 112 (2010): 1099-1114.
  38. Walz W. “Role of glial cells in the regulation of the brain ion microenvironment”. Progress in Neurobiology 33 (1989): 309-333.
  39. Yamamoto T and Hirano,A. “A comparative study of modified Bielschowsky, Bodian and thioflavin S stains on Alzheimer’s neurofibrillary tangles”. Neuropathology and Applied Neurobiology 12 (1986): 3-9.
  40. Yang I., et al. “The role of microglia in central nervous system immunity and glioma immunology”. Journal of Clinical Neuroscience 17 (2010): 6-10.
Citation: Anne K Vehmas. “Microglia and Astrocytes in Postmortem Human Brain Increase in Parallel with Aging”. EC Neurology 14.1 (2022): 21-29.

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