Defined astrocytic expression of human amyloid precursor protein in Tg2576 mouse brain. Issue 2 (28th November 2018)

• Record Type: Journal Article
• Authors: Heiland, Tina; Zeitschel, Ulrike; Puchades, Maja A.; Kuhn, Peer‐Hendrik; Lichtenthaler, Stefan F.; Bjaalie, Jan G.; Hartlage‐Rübsamen, Maike; Roßner, Steffen; Höfling, Corinna
• Is Part Of: Glia. Volume 67:Issue 2(2019)
• Page Start: 393
• Page End: 403
• Publication Date: 2018-11-28
• Subjects: Alzheimer's disease -- astrocytes -- human APP Swedish -- microglia -- oligodendrocytes -- primary neuronal and glial cultures -- Tg2576 mice; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23550
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: Transgenic Tg2576 mice expressing human amyloid precursor protein (hAPP) with the Swedish mutation are among the most frequently used animal models to study the amyloid pathology related to Alzheimer's disease (AD). The transgene expression in this model is considered to be neuron‐specific. Using a novel hAPP‐specific antibody in combination with cell type‐specific markers for double immunofluorescent labelings and laser scanning microscopy, we here report that—in addition to neurons throughout the brain—astrocytes in the corpus callosum and to a lesser extent in neocortex express hAPP. This astrocytic hAPP expression is already detectable in young Tg2576 mice before the onset of amyloid pathology and still present in aged Tg2576 mice with robust amyloid pathology in neocortex, hippocampus, and corpus callosum. Surprisingly, hAPP immunoreactivity in cortex is restricted to resting astrocytes distant from amyloid plaques but absent from reactive astrocytes in close proximity to amyloid plaques. In contrast, neither microglial cells nor oligodendrocytes of young or aged Tg2576 mice display hAPP labeling. The astrocytic expression of hAPP is substantiated by the analyses of hAPP mRNA and protein expression in primary cultures derived from Tg2576 offspring. We conclude that astrocytes, in particular in corpus callosum, may contribute to amyloid pathology in Tg2576 mice and thus mimic this aspect of AD pathology. Main Points: Young and aged Tg2576 mice express human APP not only in neurons, but also in astrocytes. Human APP mRNA and protein expression is also demonstrated in primary Tg2576 astrocytic cultures. Astrocytes may contribute to amyloid pathology in Tg2576 mice. Illustration of human APP expression (hAPP; red fluorescence) by astrocytes (GFAP, green fluorescence) in parietal cortex of an 18‐month‐old Tg2576 mouse. Note that astrocytic hAPP immunoreactivity as indicated by yellow color is limited to resting astrocytes distant from (arrows) and close to (arrowhead) amyloid plaques (asterisk), but absent from astrocytes of reactive morphology.