title: Stage-specific changes in neurogenic and glial markers in Alzheimer's disease.
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.
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, United Kingdom. Electronic address: antigoni.ekonomou@kcl.ac.uk.
authors.forename: Antigoni
authors.initials: A
authors.lastname: Ekonomou
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors.forename: George M
authors.initials: GM
authors.lastname: Savva
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Carol
authors.initials: C
authors.lastname: Brayne
authors.affiliation: Sheffield Institute for Translational Neuroscience, Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Gillian
authors.initials: G
authors.lastname: Forster
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, United Kingdom.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Francis
authors.affiliation: Institute for Ageing and Health, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Mary
authors.initials: M
authors.lastname: Johnson
authors.affiliation: Institute for Ageing and Health, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Perry
authors.affiliation: Institute for Ageing and Health, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Johannes
authors.initials: J
authors.lastname: Attems
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, United Kingdom.
authors.forename: Alyma
authors.initials: A
authors.lastname: Somani
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, United Kingdom.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Minger
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, United Kingdom.
authors.forename: Clive G
authors.initials: CG
authors.lastname: Ballard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D002452:Cell Count; D018891:Dentate Gyrus / Q000473:pathology*; D006801:Humans; D020547:Lateral Ventricles / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins
keywords: Alzheimer’s disease; Glia; Human brain; Neural progenitors; Neurogenesis; Tangles