title: Characterization of amyloid-β granules in the hippocampus of SAMP8 mice.
abstract: The senescence accelerated mouse-prone 8 (SAMP8) strain of mice is an experimental model of accelerated senescence that has also been proposed as a model of Alzheimer's disease as it shares several features with this dementia. We have recently reported amyloid-β (Aβ) granules in the hippocampus of SAMP8 mice, which contain Aβ42 and Aβ40 peptides and other amyloid-β protein precursor fragments. These granules appear clustered mainly in the stratum radiatum of the CA1 region and increase in number and size with age. Here we performed several studies to examine whether the Aβ granules in the hippocampus of SAMP8 mice contain other proteins characteristic of neuropathological aggregates, such as tau, MAP2, and α-synuclein. Moreover, we examined whether the Aβ granules in the hippocampus correspond to heparan sulphate proteoglycan (HSPG) positive granules previously described in this animal model. The results showed that Aβ granules correspond to the HSPG granular structures, being syndecan-2, a protein involved in the remodeling of dendritic spines, the type of HSPG found. Tau and MAP2, but not α-synuclein depositions, were also found in Aβ aggregates. Granules do not appear to have an astrocytic origin, since although some Aβ clusters are associated with astrocyte processes, most clusters are not. On the other hand, the presence of tau, MAP2, and NeuN in Aβ granules suggests a neuronal origin. As the components identified in Aβ granules are characteristic of the aggregates present in some neurodegenerative diseases, the SAMP8 model seems to be appropriate for the study of the processes involved in these pathologies.
authors: Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain.
authors: Gemma
authors: G
authors: Manich
authors: Clara
authors: C
authors: Mercader
authors: Jaume
authors: J
authors: del Valle
authors: Joaquim
authors: J
authors: Duran-Vilaregut
authors: Antoni
authors: A
authors: Camins
authors: Mercè
authors: M
authors: Pallàs
authors: Jordi
authors: J
authors: Vilaplana
authors: Carme
authors: C
authors: Pelegrí
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D053669:Syndecan-2 / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D019812:Heparan Sulfate Proteoglycans; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D009419:Nerve Tissue Proteins; D016875:tau Proteins; C071927:perlecan; D053669:Syndecan-2