Region-specific neuron and synapse loss in the hippocampus of APP SL/PS1 knock-in mice

Ivona Brasnjevic, Roy Lardenoije, Christoph Schmitz, Nicolien Van Der Kolk, Dara L. Dickstein, Hisaaki Takahashi, Patrick R. Hof, Harry W.M. Steinbusch, Bart P.F. Rutten

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Transgenic mouse models with knock-in (KI) expression of human mutant amyloid precursor protein (APP) and/or human presenilin 1 (PS1) may be helpful to elucidate the cellular consequences of APP and PS1 misprocessing in the aging brain. Age-related alterations in total numbers of neurons and in numbers of synaptophysin-immunoreactive presynaptic boutons (SIPB), as well as the amyloid plaque load were analyzed in the hippocampal dentate gyrus (DG), CA3, and CA1-2 of 2- and 10-month-old APPSL/PS1 homozygous KI, APPSL (expressing human mutant APP751 carrying the Swedish [K670N/M671L] and London [V717I] mutations under Thy-1 promoter), and PS1 homozygous KI mice (expressing human PS1 mutations [M233T and L235P]). APPSL/PS1 homozygous KI mice, but neither APPSL mice nor PS1 homozygous KI mice, showed substantial agerelated loss of neurons (-47.2%) and SIPB (-22.6%), specifically in CA1-2. PS1 homozygous KI mice showed an age-related increase in hippocampal granule cell numbers (+37.9%). Loss of neurons and SIPB greatly exceeded the amount of local extracellular Aβ aggregation and astrocytes, whereas region-specific accumulation of intraneuronal Aβ preceded neuron and synapse loss. An age-related increase in the ratio of SIPB to neuron numbers in CA1-2 of APPSL/PS1 homozygous KI mice was suggestive of compensatory synaptic plasticity. These findings indicate a region-selectivity in intra- and extraneuronal Aβ accumulation in connection with neuron and synapse loss in the hippocampus of APPSL/PS1 homozygous KI mice.

Original languageEnglish
Pages (from-to)8-19
Number of pages12
JournalTranslational Neuroscience
Issue number1
StatePublished - Mar 2013


  • Alzheimer's disease
  • Amyloid precursor protein
  • Hippocampus
  • Image analysis
  • Neuron loss
  • Presenilin-1
  • Stereology
  • Synapse loss


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