title: Clustering of plaques contributes to plaque growth in a mouse model of Alzheimer's disease.
abstract: Amyloid-β (Aβ) plaque deposition plays a central role in the pathogenesis of Alzheimer's disease (AD). Post-mortem analysis of plaque development in mouse models of AD revealed that plaques are initially small, but then increase in size and become more numerous with age. There is evidence that plaques can grow uniformly over time; however, a complementary hypothesis of plaque development is that small plaques cluster and grow together thereby forming larger plaques. To investigate the latter hypothesis, we studied plaque formation in APPPS1 mice using in vivo two-photon microscopy and immunohistochemical analysis. We used sequential pre- and post-mortem staining techniques to label plaques at different stages of development and to detect newly emerged plaques. Post-mortem analysis revealed that a subset (22 %) of newly formed plaques appeared very close (<40 μm) to pre-existing plaques and that many close plaques (25 %) that were initially separate merged over time to form one single large plaque. Our results suggest that small plaques can cluster together, thus forming larger plaques as a complementary mechanism to simple uniform plaque growth from a single initial plaque. This study deepens our understanding of Aβ deposition and demonstrates that there are multiple mechanisms at play in plaque development.
authors.affiliation: Adolf Butenandt Institute, Biochemistry, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Joanna F
authors.initials: JF
authors.lastname: McCarter
authors.forename: Sabine
authors.initials: S
authors.lastname: Liebscher
authors.forename: Teresa
authors.initials: T
authors.lastname: Bachhuber
authors.forename: Claudia
authors.initials: C
authors.lastname: Abou-Ajram
authors.forename: Mark
authors.initials: M
authors.lastname: Hübener
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.forename: Christian
authors.initials: C
authors.lastname: Haass
authors.forename: Melanie
authors.initials: M
authors.lastname: Meyer-Luehmann
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods
chemical_list: D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1