Brain Region-Specific Differences in Amyloid-β Plaque Composition in 5XFAD Mice

Area of Science:

• Neuroscience
• Pathology
• Biochemistry

Background:

• Senile plaques of amyloid-beta (Aβ) are key Alzheimer's disease (AD) hallmarks.
• Aβ peptides exhibit length heterogeneity, with Aβ1-40 and Aβ1-42 often considered full-length.
• Understanding Aβ species distribution is crucial for AD pathogenesis research.

Purpose of the Study:

• To investigate the distribution and age-dependent changes of different Aβ species in the brains of 5XFAD mice.
• To analyze the dynamics of full-length (Aβ1-x) and N-terminally truncated (Aβ4-x) Aβ peptides in amyloid deposits.
• To explore potential plaque remodeling processes in specific brain regions.

Main Methods:

• Immunohistochemistry was employed to detect and quantify various Aβ species.
• Analysis focused on amyloid deposits in the subiculum, hippocampus, and cortex of 5XFAD mice across different ages.
• Quantification of Aβ1-x, Aβx-42, and Aβ4-x species distribution was performed.

Main Results:

• Plaque load increased in all analyzed brain regions, with the subiculum showing the highest relative coverage.
• In the subiculum, Aβ1-x load peaked at five months and subsequently declined.
• Conversely, N-terminally truncated Aβ4-x species density increased continuously with age in all regions.

Conclusions:

• Alzheimer's disease amyloid plaques likely undergo remodeling, involving the conversion of deposited Aβ1-x peptides.
• N-terminally truncated Aβ4-x species accumulate over time, particularly in brain regions with high plaque burden.
• These findings suggest a dynamic process of plaque evolution in the aging AD brain.