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Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
Published on: June 26, 2018
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Formic acid impairs α-synuclein seeding activity in human and mouse brains.
Biorxiv : the Preprint Server for Biology
|August 12, 2025
Summary
Formic acid treatment effectively reduces the risk of occupational exposure to alpha-synuclein (α-syn) aggregates in fixed brain samples. This method inactivates the seeding activity of pathological α-syn without compromising histopathology.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Alpha-synuclein (α-syn) aggregates form neuropathological inclusions in synucleinopathies.
- The mouse-human transmission barrier for α-syn is lower than previously thought, increasing occupational exposure risks.
- Standard tissue fixation methods do not eliminate the seeding activity of pathological α-syn.
Purpose of the Study:
- To evaluate the efficacy of formic acid treatment in reducing α-syn seeding activity in fixed human and mouse brain samples.
- To determine if formic acid treatment preserves the quality of histopathological analysis.
Main Methods:
- Treatment of paraformaldehyde-fixed brain samples from dementia with Lewy bodies patients and α-syn pre-formed fibrils (PFF)-injected mice with 96% formic acid.
- Assessment of α-syn seeding activity using real-time quaking-induced conversion (RT-QuIC).
- Evaluation of histopathological features and immunostaining quality post-treatment.
Main Results:
- Formic acid treatment reduced α-syn seeding dose by 6 and 8 logarithms in DLB and mouse brains, respectively.
- RT-QuIC reactions showed significantly longer lag phases and decreased fluorescence with formic acid-treated samples.
- Histopathological features and immunostaining quality were preserved in formic acid-treated tissues.
Conclusions:
- Formic acid treatment is a rapid and effective method for reducing α-syn seeding activity in fixed brain samples.
- This procedure significantly lowers the risk of accidental laboratory exposure to pathological α-syn.
- Histopathological analysis quality is maintained after formic acid treatment.
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