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Lookup NU author(s): Professor Carol Brayne, Mary Johnson, Emeritus Professor Elaine Perry, Professor Johannes Attems, Dr Clive Ballard
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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.
Author(s): Ekonomou A, Savva GM, Brayne C, Forster G, Francis PT, Johnson M, Perry EK, Attems J, Somani A, Minger SL, Ballard CG, on behalf of The Medical Research Council Cognitive Function and Ageing Neuropathology Study
Publication type: Article
Publication status: Published
Journal: Biological Psychiatry
Year: 2015
Volume: 77
Issue: 8
Pages: 711-719
Print publication date: 15/04/2015
Online publication date: 09/06/2014
Acceptance date: 23/05/2014
ISSN (print): 0006-3223
ISSN (electronic): 1873-2402
Publisher: Elsevier
URL: http://dx.doi.org/10.1016/j.biopsych.2014.05.021
DOI: 10.1016/j.biopsych.2014.05.021
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