Brain Structure and Function

, Volume 214, Issue 2, pp 145–160

Hippocampal interneuron loss in an APP/PS1 double mutant mouse and in Alzheimer’s disease

  • Hisaaki Takahashi
  • Ivona Brasnjevic
  • Bart P. F. Rutten
  • Nicolien Van Der Kolk
  • Daniel P. Perl
  • Constantin Bouras
  • Harry W. M. Steinbusch
  • Christoph Schmitz
  • Patrick R. Hof
  • Dara L. Dickstein
Original article

DOI: 10.1007/s00429-010-0242-4

Cite this article as:
Takahashi, H., Brasnjevic, I., Rutten, B.P.F. et al. Brain Struct Funct (2010) 214: 145. doi:10.1007/s00429-010-0242-4

Abstract

Hippocampal atrophy and neuron loss are commonly found in Alzheimer’s disease (AD). However, the underlying molecular mechanisms and the fate in the AD hippocampus of subpopulations of interneurons that express the calcium-binding proteins parvalbumin (PV) and calretinin (CR) has not yet been properly assessed. Using quantitative stereologic methods, we analyzed the regional pattern of age-related loss of PV- and CR-immunoreactive (ir) neurons in the hippocampus of mice that carry M233T/L235P knocked-in mutations in presenilin-1 (PS1) and overexpress a mutated human beta-amyloid precursor protein (APP), namely, the APPSL/PS1 KI mice, as well as in APPSL mice and PS1 KI mice. We found a loss of PV-ir neurons (40–50%) in the CA1-2, and a loss of CR-ir neurons (37–52%) in the dentate gyrus and hilus of APPSL/PS1 KI mice. Interestingly, comparable PV- and CR-ir neuron losses were observed in the dentate gyrus of postmortem brain specimens obtained from patients with AD. The loss of these interneurons in AD may have substantial functional repercussions on local inhibitory processes in the hippocampus.

Keywords

Alzheimer’s diseaseAmyloid precursor proteinCalcium-binding proteinsHippocampusPresenilin-1Stereology

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Hisaaki Takahashi
    • 1
    • 2
    • 3
  • Ivona Brasnjevic
    • 1
    • 2
    • 4
  • Bart P. F. Rutten
    • 1
    • 2
    • 4
  • Nicolien Van Der Kolk
    • 1
    • 2
    • 4
  • Daniel P. Perl
    • 5
    • 6
  • Constantin Bouras
    • 6
    • 7
  • Harry W. M. Steinbusch
    • 1
    • 2
    • 4
  • Christoph Schmitz
    • 1
    • 2
    • 4
    • 6
  • Patrick R. Hof
    • 6
  • Dara L. Dickstein
    • 6
  1. 1.Department of NeuroscienceMaastricht UniversityMaastrichtThe Netherlands
  2. 2.Department of Psychiatry and NeuropsychologyMaastricht UniversityMaastrichtThe Netherlands
  3. 3.Department of Molecular and Cellular Physiology, Graduate School of MedicineEhime UniversityMatsuyamaJapan
  4. 4.European Graduate School of Neuroscience (EURON)MaastrichtThe Netherlands
  5. 5.Department of Pathology (Neuropathology)Mount Sinai School of MedicineNew YorkUSA
  6. 6.Department of Neuroscience, Kastor Neurobiology of Aging LaboratoriesMount Sinai School of MedicineNew YorkUSA
  7. 7.Department of PsychiatryUniversity of Geneva School of MedicineGenevaSwitzerland