The age-related slow increase in amyloid pathology in APP.V7171 mice activates microglia, but does not alter hippocampal neurogenesis

NEUROBIOLOGY OF AGING

卷:61

Article

Hoeijmakers, Lianne¹  Meerhoff, Gideon F.¹  de Vries, Janneke W.¹  Ruigrok, Silvie R.¹  van Dam, Anne-Marie²  van Leuven, Fred³  Korosi, Aniko¹  Lucassen, Paul J.¹ 

[1] Univ Amsterdam, Swammerdam Inst Life Sci, Brain Plast Grp, Ctr Neurosci, Sci Pk 904, NL-1098 XH Amsterdam, Netherlands

[2] Vrije Univ Amsterdam, Med Ctr, Dept Anat & Neurosci, Amsterdam Neurosci, Amsterdam, Netherlands

[3] Univ Leuven, LEGTEGG, Expt Genet Grp, Leuven, Belgium

关键词: APP;    Neuroinflammation;    Neurogenesis;    Doublecortin;    Calretinin;    Alzheimer's disease;    Aging;   

DOI  :  10.1016/j.neurobiolaging.2017.09.013

来源: Elsevier

【 摘 要 】

In Alzheimer's disease, the hippocampus is characterized by abundant deposition of amyloid peptides (amyloid beta [A beta]) and neuroinflammation. Adult hippocampal neurogenesis (AHN) is a form of plasticity that contributes to cognition and can be influenced by either or both pathology and neuroinflammation. Their interaction has been studied before in rapidly progressing transgenic mouse models with strong overexpression of amyloid precursor protein (APP) and/or presenilin 1. So far, changes in AHN and neuroinflammation remain poorly characterized in slower progressing models at advanced age, which approach more closely sporadic Alzheimer's disease. Here, we analyzed 10- to 26-month-old APP.V7171 mice for possible correlations between A beta pathology, microglia, and AHN. The age-related increase in amyloid pathology was closely paralleled by microglial CD68 upregulation, which was largely absent in age-matched wild-type littermates. Notably, aging reduced the AHN marker doublecortin, but not cal retinin, to a similar extent in wild-type and APP.V7171 mice between 10 and 26 months. This demonstrates that AHN is influenced by advanced age in the APP.V7171 mouse model, but not by A beta and microglial activation. (C) 2017 Elsevier Inc. All rights reserved.

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