Related Experiment Video
Updated: Jan 29, 2026
09:22
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
19.0K
Site-Specific Aspartic Acid d-Isomerization in Tau R2 and R3 Peptide Seeds Attenuates Seed-Induced Fibril Formation
Genta Ito1, Takuya Murata1, Noriko Isoo2
1Department of Biomolecular Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo 173-8605, Japan.
Biomolecules
|January 28, 2026
Summary
Alzheimer's disease tau seeds with a specific modification (d-isomerization) show reduced ability to spread pathology. This suggests natural changes in tau seeds may slow Alzheimer's disease progression.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Tau protein aggregation is central to Alzheimer's disease (AD) pathology.
- Pathology spread is hypothesized to occur via prion-like tau seeds.
- Aggregated tau in AD brains contains age-related d-isomerized aspartic acid (d-Asp).
Purpose of the Study:
- Investigate the impact of site-specific d-isomerization on tau seed activity.
- Determine how d-Asp modification affects tau fibril formation and propagation.
Main Methods:
- Studied site-specific d-isomerization in R2 and R3 tau repeat-domain peptides.
- Assessed seeding activity using in vitro fibrillization assays.
- Validated findings in a cellular model of tau aggregation.
Main Results:
- Stereochemical integrity of tau peptides is critical for seeding function.
- d-isomerization at Asp314 in R3 peptide seeds significantly impaired templating of full-length tau fibrillization.
- R3 seeds with d-Asp314 were less potent in inducing phosphorylated tau aggregates in cells.
Conclusions:
- Asp d-isomerization in tau seeds attenuates their pathological seeding activity.
- This spontaneous modification may intrinsically modulate Alzheimer's disease progression.
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