Stage-Specific Changes in Neurogenic and Glial Markers in Alzheimer's Disease

Antigoni Ekonomou, George M. Savva, Carol Brayne, Gillian Forster, Paul T. Francis, Mary Johnson, Elaine K. Perry, Johannes Attems, Alyma Somani, Stephen L. Minger, Clive G. Ballard

Research output: Contribution to journalArticle

Abstract

Background: Reports of altered endogenous neurogenesis in people with Alzheimer's disease (AD) and transgenic AD models have suggested that endogenous neurogenesis may be an important treatment target, but there is considerable discrepancy among studies. We examined endogenous neurogenesis and glia changes across the range of pathologic severity of AD in people with and without dementia to address this key question. Methods: Endogenous neurogenesis and glia in the subventricular zone and dentate gyrus neurogenic niches were evaluated using single and double immunohistochemistry and a validated antibody selection for stage-specific and type-specific markers in autopsy tissue from a representative cohort of 28 participants in the Medical Research Council Cognitive Function and Ageing Study. Immunopositive cells were measured blinded to diagnosis using bright-field and fluorescent microscopy. Results: The number of newly generated neurons significantly declined only in the dentate gyrus of patients with severe tau pathology. No other changes in other neurogenic markers were observed in either of the neurogenic niches. Alterations in astrocytes and microglia were also observed in the dentate gyrus across the different stages of tau pathology. No change in any of the markers was observed in individuals who died with dementia compared with individuals who did not die with dementia. Conclusions: Alterations in endogenous neurogenesis appeared to be confined to a reduction in the generation of new neurons in the dentate gyrus of patients with AD and severe neurofibrillary tangle pathology and were accompanied by changes in the glia load. These data suggest that intervention enhancing endogenous neurogenesis may be a potential therapeutic target in AD. Crown
Original languageEnglish
Pages (from-to)711–719
JournalBiological Psychiatry
Volume77
Issue number8
Early online date9 Jun 2014
DOIs
Publication statusPublished - 15 Apr 2015

Keywords

  • Alzheimer's disease
  • glia
  • human brain
  • neural progenitors
  • neurogenesis
  • tangles

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