Original article

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 TakahashiAffiliated withDepartment of Neuroscience, Maastricht UniversityDepartment of Psychiatry and Neuropsychology, Maastricht UniversityDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University
  • , Ivona BrasnjevicAffiliated withDepartment of Neuroscience, Maastricht UniversityDepartment of Psychiatry and Neuropsychology, Maastricht UniversityEuropean Graduate School of Neuroscience (EURON)
  • , Bart P. F. RuttenAffiliated withDepartment of Neuroscience, Maastricht UniversityDepartment of Psychiatry and Neuropsychology, Maastricht UniversityEuropean Graduate School of Neuroscience (EURON)
  • , Nicolien Van Der KolkAffiliated withDepartment of Neuroscience, Maastricht UniversityDepartment of Psychiatry and Neuropsychology, Maastricht UniversityEuropean Graduate School of Neuroscience (EURON)
  • , Daniel P. PerlAffiliated withDepartment of Pathology (Neuropathology), Mount Sinai School of MedicineDepartment of Neuroscience, Kastor Neurobiology of Aging Laboratories, Mount Sinai School of Medicine
  • , Constantin BourasAffiliated withDepartment of Neuroscience, Kastor Neurobiology of Aging Laboratories, Mount Sinai School of MedicineDepartment of Psychiatry, University of Geneva School of Medicine
  • , Harry W. M. SteinbuschAffiliated withDepartment of Neuroscience, Maastricht UniversityDepartment of Psychiatry and Neuropsychology, Maastricht UniversityEuropean Graduate School of Neuroscience (EURON)
  • , Christoph SchmitzAffiliated withDepartment of Neuroscience, Maastricht UniversityDepartment of Psychiatry and Neuropsychology, Maastricht UniversityEuropean Graduate School of Neuroscience (EURON)Department of Neuroscience, Kastor Neurobiology of Aging Laboratories, Mount Sinai School of Medicine
  • , Patrick R. HofAffiliated withDepartment of Neuroscience, Kastor Neurobiology of Aging Laboratories, Mount Sinai School of Medicine
    • , Dara L. DicksteinAffiliated withDepartment of Neuroscience, Kastor Neurobiology of Aging Laboratories, Mount Sinai School of Medicine Email author 

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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 disease Amyloid precursor protein Calcium-binding proteins Hippocampus Presenilin-1 Stereology