Hippocampal interneuron loss in an APP/PS1 double mutant mouse and in Alzheimer's disease.
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 APP(SL)/PS1 KI mice, as well as in APP(SL) 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 APP(SL)/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.
Takahashi
Hisaaki
H
Department of Neuroscience, Maastricht University, 6200 MD, Maastricht, The Netherlands.
Brasnjevic
Ivona
I
Rutten
Bart P F
BP
Van Der Kolk
Nicolien
N
Perl
Daniel P
DP
Bouras
Constantin
C
Steinbusch
Harry W M
HW
Schmitz
Christoph
C
Hof
Patrick R
PR
Dickstein
Dara L
DL
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D064032:Calbindin 2; D002452:Cell Count; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D055879:Gene Knock-In Techniques; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007395:Interneurons / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009433:Neural Inhibition / Q000235:genetics; D010320:Parvalbumins / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; C576764:CALB2 protein, human; C576511:Calb2 protein, mouse; D064032:Calbindin 2; D010320:Parvalbumins; D053764:Presenilin-1; D064030:S100 Calcium Binding Protein G