ArticleBrain pathology (Zurich, Switzerland)2022
Multiple system atrophy variant with severe hippocampal pathology.
Article in Brain pathology (Zurich, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Autonomic dysfunction in multiple system atrophy: from pathophysiology to clinical manifestations.Annals of medicine · 2025Review
- Lewy-MSA hybrid fold drives distinct neuronal α-synuclein pathology.Communications biology · 2025Article
- Identical Seeding Characteristics and Cryo-EM Filament Structures in FTLD-Synuclein and Typical Multiple System Atrophy.Neuropathology and applied neurobiology · 2025Article
- The Spectrum of Cognitive Impairment in Atypical Parkinsonism Syndromes: A Comprehensive Review of Current Understanding and Research.Diseases (Basel, Switzerland) · 2025Review
- Co-pathologies modify hippocampal protein accumulation patterns in neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- α-synuclein and tau: interactions, cross-seeding, and the redefinition of synucleinopathies as complex proteinopathies.Frontiers in neuroscience · 2025Review
- From Perspective of Hippocampal Plasticity: Function of Antidepressant Chinese Medicine Xiaoyaosan.Chinese journal of integrative medicine · 2024Review
- Article
- Degeneration of olivospinal tract in the upper cervical spinal cord of multiple system atrophy patients: Reappraisal of Helweg's triangular tract.Brain pathology (Zurich, Switzerland) · 2024Article
- Multiple system atrophy with amyloid-β-predominant Alzheimer's disease neuropathologic change.Brain communications · 2024Article
- Characteristics of Mild Cognitive Impairment and Associated Factors in MSA Patients.Brain sciences · 2023Article
- Association between Cognitive Impairment and Hippocampal Subfield Volumes in Multiple System Atrophy.Parkinson's disease · 2023Article
- Multiple system atrophy with hippocampal pathology.Brain pathology (Zurich, Switzerland) · 2022Article
- A NAC domain mutation (E83Q) unlocks the pathogenicity of human alpha-synuclein and recapitulates its pathological diversity.Science advances · 2022Article
- Long-standing multiple system atrophy-Parkinsonism with limbic and FTLD-type α-synuclein pathology.Neuropathology and applied neurobiology · 2022Article
- Heterogeneity of Multiple System Atrophy: An Update.Biomedicines · 2022Review
- Multiple system atrophy variant with severe hippocampal pathology.Brain pathology (Zurich, Switzerland) · 2022Article
- Neuropathology and molecular diagnosis of Synucleinopathies.Molecular neurodegeneration · 2021Review
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Authors and funding
29 authors at 10 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The striatonigral and olivopontocerebellar systems are known to be vulnerable in multiple system atrophy (MSA), showing neuronal loss, astrogliosis, and alpha-synuclein-immunoreactive inclusions. 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-quantitative analysis of anti-alpha-synuclein 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, p = 0.0324), longer disease duration (13.1 ± 5.9 years; Mann-Whitney U-test, p = 0.000157), higher prevalence of cognitive impairment (four patients; Fisher's exact test, p = 0.0222), and lower brain weight (1070.3 ± 168.6 g; Mann-Whitney U-test, p = 0.00911) than other patients. The hippocampal granule cells and cornu ammonis area 1/subiculum almost always showed severe NCIs. The NCIs appeared to be ring-shaped or neurofibrillary tangle-like, fibrous configurations. Three of 12 patients also had dense, round-shaped NCIs that were morphologically similar to pick bodies. The patients with Pick body-like 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-43 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-synucleinopathy in the pathogenesis of MSA.
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