Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer's disease.
According to the "amyloid hypothesis of Alzheimer's disease," beta-amyloid is the primary driving force in Alzheimer's disease pathogenesis. Despite the development of many transgenic mouse lines developing abundant beta-amyloid-containing plaques in the brain, the actual link between amyloid plaques and neuron loss has not been clearly established, as reports on neuron loss in these models have remained controversial. We investigated transgenic mice expressing human mutant amyloid precursor protein APP751 (KM670/671NL and V717I) and human mutant presenilin-1 (PS-1 M146L). Stereologic and image analyses revealed substantial age-related neuron loss in the hippocampal pyramidal cell layer of APP/PS-1 double-transgenic mice. The loss of neurons was observed at sites of Abeta aggregation and surrounding astrocytes but, most importantly, was also clearly observed in areas of the parenchyma distant from plaques. These findings point to the potential involvement of more than one mechanism in hippocampal neuron loss in this APP/PS-1 double-transgenic mouse model of Alzheimer's disease.
Schmitz
Christoph
C
Department of Psychiatry and Neuropsychology, Division of Cellular Neuroscience, University of Maastricht, Maastricht, The Netherlands. c.schmitz@np.unimaas.nl
Rutten
Bart P F
BP
Pielen
Andrea
A
Schäfer
Stephanie
S
Wirths
Oliver
O
Tremp
Günter
G
Czech
Christian
C
Blanchard
Veronique
V
Multhaup
Gerd
G
Rezaie
Payam
P
Korr
Hubert
H
Steinbusch
Harry W M
HW
Pradier
Laurent
L
Bayer
Thomas A
TA
D000375:Aging; D000544:Alzheimer Disease / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis / Q000473:pathology; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000473:pathology*; D058225:Plaque, Amyloid / Q000473:pathology*
D016564:Amyloid beta-Protein Precursor