Presenilin-1 familial Alzheimer's disease mutation alters hippocampal neurogenesis and memory function in CCL2 null mice

Tomomi Kiyota, Christine M. Morrison, Guihua Tu, Bhagyalaxmi Dyavarshetty, Robert A. Weir, Gang Zhang, Huangui Xiong, Howard E. Gendelman

Research output: Contribution to journalArticle

12 Scopus citations


Aberrations in hippocampal neurogenesis are associated with learning and memory, synaptic plasticity and neurodegeneration in Alzheimer's disease (AD). However, the linkage between them, β-amyloidosis and neuroinflammation is not well understood. To this end, we generated a mouse overexpressing familial AD (FAD) mutant human presenilin-1 (PS1) crossed with a knockout (KO) of the CC-chemokine ligand 2 (CCL2) gene. The PS1/CCL2KO mice developed robust age-dependent deficits in hippocampal neurogenesis associated with impairments in learning and memory, synaptic plasticity and long-term potentiation. Neurogliogenesis gene profiling supported β-amyloid independent pathways for FAD-associated deficits in hippocampal neurogenesis. We conclude that these PS1/CCL2KO mice are suitable for studies linking host genetics, immunity and hippocampal function.

Original languageEnglish (US)
Pages (from-to)311-321
Number of pages11
JournalBrain, Behavior, and Immunity
StatePublished - Oct 1 2015



  • Chemokine
  • Hippocampus
  • Long-term potentiation
  • Morris water maze
  • Neurogliogenesis

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this