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Multiple system atrophy variant with severe hippocampal pathology.

Takashi Ando1,2, Yuichi Riku1,2, Akio Akagi2

  • 1Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Brain Pathology (Zurich, Switzerland)
|July 13, 2021
PubMed
Summary

This study identifies a distinct pathological variant of multiple system atrophy (MSA) characterized by significant hippocampal involvement. This finding highlights the role of alpha-synuclein in MSA pathogenesis and suggests potential diagnostic implications.

Keywords:
alpha-synucleindementiahippocampusmultiple system atrophyneuronal inclusions

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Area of Science:

  • Neuropathology
  • Neurodegenerative Diseases
  • Alpha-synucleinopathies

Background:

  • Multiple system atrophy (MSA) typically affects the striatonigral and olivopontocerebellar systems, characterized by neuronal loss, astrogliosis, and alpha-synuclein inclusions.
  • Rare variants of MSA involve neuronal cytoplasmic inclusions (NCIs) outside these typical regions.
  • The clinical and pathological spectrum of MSA continues to expand, necessitating detailed characterization of atypical presentations.

Purpose of the Study:

  • To investigate the clinical and pathological features of MSA patients with prominent hippocampal involvement.
  • To determine the prevalence and characteristics of alpha-synuclein pathology within the hippocampus in MSA.
  • To explore potential correlations between severe hippocampal pathology and clinical phenotypes in MSA.

Main Methods:

  • Retrospective analysis of 146 consecutively autopsied MSA patients.
  • Semi-quantitative immunohistochemistry for alpha-synuclein to assess NCIs in specific brain regions, including the hippocampus.
  • Clinical data review, including disease duration, cognitive status, and brain weight.
  • Statistical analysis (Fisher's exact test, Mann-Whitney U-test) to compare patient groups.

Main Results:

  • Twelve out of 146 MSA patients (8.2%) exhibited severe NCIs in hippocampal regions (granule cells, cornu ammonis, parahippocampal gyrus, amygdala).
  • Patients with severe hippocampal involvement showed a higher prevalence of women, longer disease duration, increased cognitive impairment, and lower brain weight.
  • NCIs in the hippocampus were often ring-shaped or neurofibrillary tangle-like; a subset displayed Pick body-like morphology. Minimal tau and TDP-43 pathology was observed.

Conclusions:

  • A distinct pathological variant of MSA characterized by severe hippocampal neuron involvement is identified.
  • This hippocampal MSA phenotype is associated with specific demographic and clinical features, including cognitive impairment.
  • The findings underscore the significance of alpha-synucleinopathy in the hippocampus for MSA pathogenesis and suggest this variant may represent a unique clinicopathological entity.