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Related Experiment Video

Updated: Feb 21, 2026

Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains
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Alpha-synucleinopathies.

Irina Alafuzoff1, Päivi Hartikainen2

  • 1Department of Immunology, Genetics and Pathology, Uppsala University, Department of Pathology, Uppsala University Hospital and Rudbeck Laboratory, Uppsala, Sweden.

Handbook of Clinical Neurology
|October 9, 2017
PubMed
Summary

Alpha-synucleinopathies (αS-pathies) are neurodegenerative disorders characterized by altered alpha-synuclein (αS) in the brain. Diagnosis currently relies on postmortem examination, focusing on αS detection and its distribution.

Keywords:
Braak stagingLewy bodiesMcKeith stagingParkinson diseaseParkinson disease with dementiadementia with Lewy bodiesmultiple-system atrophyα-synuclein

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Area of Science:

  • Neuropathology
  • Neurodegenerative Diseases
  • Biomarker Research

Background:

  • Alpha-synucleinopathy (αS-pathy) encompasses disorders like Parkinson disease, characterized by altered αS in brain tissue.
  • Current definitive diagnosis requires postmortem examination, despite ongoing research into in-vivo imaging and fluid biomarkers.
  • Neurodegenerative disease progression often follows predictable neuroanatomic distribution patterns.

Purpose of the Study:

  • To outline the neuropathological diagnostic criteria for αS-pathy.
  • To highlight the role of immunohistochemistry and staging in diagnosing αS-pathy.
  • To discuss the current limitations and future directions in αS-pathy diagnosis.

Main Methods:

  • Immunohistochemistry using antibodies against αS for tissue analysis.
  • Assessment of neuroanatomic distribution of αS pathology using staging systems (e.g., Braak, McKeith).
  • Review of current diagnostic practices and emerging technologies for αS-pathy.

Main Results:

  • Neuropathological diagnosis of αS-pathy is based on detecting altered αS and its distribution in brain tissue.
  • Immunohistochemistry has been a standard diagnostic method since the 1980s.
  • Clinicopathological correlation can be complicated by incidental or concomitant αS pathology.

Conclusions:

  • Definitive diagnosis of αS-pathy currently relies on postmortem neuropathological examination.
  • Detection and staging of αS pathology are crucial for neuropathological diagnosis.
  • Future diagnostic approaches may incorporate advanced imaging and fluid-based biomarkers.