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Brains of SAMP8 mice reveal an age\u2010associated increase of PAS\u2010positive granular structures in the hippocampal formation and astrogliosis in the brain stem and hippocampus. A spongy degeneration in the brain stem appears at 1 month of age and reaches a maximum at 4\u20108 months. In addition, clusters of activated microglia also appear around the vacuoles in the brain stem. \u03b2\/A4(A\u03b2) protein\u2010like immunoreactive granular structures are observed in various regions and increase in number markedly with age. Other age\u2010associated histological changes include cortical atrophy, neuronal cell loss in locus coeruleus and lateral tegmental nuclei, intraneuronal accumulation of lipopigments in Purkinje cells and eosinophilic inclusion bodies in thalamic neurons. A blood\u2013brain barrier dysfunction and astrogliosis are also prominent with advancing age in the hippocampus. These changes are generally similar to the pathomorphology of aging human brains and characterized by their association with some specific glioneuronal reactions. As for the hallmarks of Alzheimer brains, tau morphology has not yet been confirmed regardless of the age\u2010related increase in phosphorylated tau in SAMP8 mice brains, but early age\u2010related A\u03b2 deposition in the hippocampus has recently been published. SAMP8 mice are, therefore, not only a senescence\u2010accelerated model but also a promising model for Alzheimer's disease and other cognitive disorders.<\/jats:p>","DOI":"10.1111\/neup.12373","type":"journal-article","created":{"date-parts":[[2017,3,6]],"date-time":"2017-03-06T04:28:36Z","timestamp":1488774516000},"page":"293-305","source":"Crossref","is-referenced-by-count":164,"title":["SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2091-2720","authenticated-orcid":false,"given":"Ichiro","family":"Akiguchi","sequence":"first","affiliation":[{"name":"Center of Neurological and Cerebrovascular Diseases, Koseikai Takeda Hospital  Kyoto Japan"},{"name":"Department of Health Science Kyoto Koka Women's University  Kyoto 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