title: Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Psychiatry and Neuropsychology, Division of Cellular Neuroscience, University of Maastricht, Maastricht, The Netherlands. c.schmitz@np.unimaas.nl
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmitz
authors.forename: Bart P F
authors.initials: BP
authors.lastname: Rutten
authors.forename: Andrea
authors.initials: A
authors.lastname: Pielen
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schäfer
authors.forename: Oliver
authors.initials: O
authors.lastname: Wirths
authors.forename: Günter
authors.initials: G
authors.lastname: Tremp
authors.forename: Christian
authors.initials: C
authors.lastname: Czech
authors.forename: Veronique
authors.initials: V
authors.lastname: Blanchard
authors.forename: Gerd
authors.initials: G
authors.lastname: Multhaup
authors.forename: Payam
authors.initials: P
authors.lastname: Rezaie
authors.forename: Hubert
authors.initials: H
authors.lastname: Korr
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: Laurent
authors.initials: L
authors.lastname: Pradier
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bayer
mesh_terms: 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*
chemical_list: D016564:Amyloid beta-Protein Precursor