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MSA patients who displayed abundant neuronal cytoplasmic inclusions (NCIs) in the regions other than the striatonigral or olivopontocerebellar system have occasionally been diagnosed with variants of MSA. In this study, we report clinical and pathologic findings of MSA patients characterized by prominent pathologic involvement of the hippocampus. We assessed 146 consecutively autopsied MSA patients. Semi\u2010quantitative analysis of anti\u2010alpha\u2010synuclein immunohistochemistry revealed that 12 of 146 patients (8.2%) had severe NCIs in two or more of the following areas: the hippocampal granule cells, cornu ammonis areas, parahippocampal gyrus, and amygdala. In contrast, the remaining 134 patients did not show severe NCIs in any of these regions. Patients with severe hippocampal involvement showed a higher representation of women (nine women\/three men; Fisher's exact test, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.0324), longer disease duration (13.1\u00a0\u00b1\u00a05.9\u00a0years; Mann\u2013Whitney U\u2010test, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.000157), higher prevalence of cognitive impairment (four patients; Fisher's exact test, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.0222), and lower brain weight (1070.3\u00a0\u00b1\u00a0168.6\u00a0g; Mann\u2013Whitney U\u2010test, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.00911) than other patients. The hippocampal granule cells and cornu ammonis area 1\/subiculum almost always showed severe NCIs. The NCIs appeared to be ring\u2010shaped or neurofibrillary tangle\u2010like, fibrous configurations. Three of 12 patients also had dense, round\u2010shaped NCIs that were morphologically similar to pick bodies. The patients with Pick body\u2010like inclusions showed more severe atrophy of the medial temporal lobes and broader spreading of NCIs than those without. Immunohistochemistry for hyperphosphorylated tau and phosphorylated TDP\u201043 revealed minimal aggregations in the hippocampus of the hippocampal MSA patients. Our observations suggest a pathological variant of MSA that is characterized by severe involvement of hippocampal neurons. This phenotype may reinforce the importance of neuronal alpha\u2010synucleinopathy in the pathogenesis of MSA.<\/jats:p>","DOI":"10.1111\/bpa.13002","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T16:33:08Z","timestamp":1626193988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Multiple system atrophy variant with severe hippocampal pathology"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7045-7098","authenticated-orcid":false,"given":"Takashi","family":"Ando","sequence":"first","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan"},{"name":"Department of Neuropathology Institute for Medical Science of Aging Aichi Medical University Nagakute 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