Basic Science and Pathogenesis

Area of Science:

• Neuroscience
• Pathology
• Biochemistry

Background:

• Alzheimer's disease (AD) is a progressive dementia characterized by amyloid-beta (Aβ) and tau pathology.
• Aβ aggregates exhibit prion-like characteristics, including strain variability.
• This heterogeneity contributes to diverse clinical and pathological presentations in AD.

Purpose of the Study:

• To investigate differences in Aβ propagation and deposition.
• To compare the effects of human and mouse Aβ inoculums in different AD mouse models.

Main Methods:

• Immunostaining and Thioflavin S (ThS) staining were employed.
• Intracerebral delivery of human and mouse brain homogenates into Tg2576 and APP/PS1 mouse models.

Main Results:

• The same Aβ inoculum induced varied Aβ pathology patterns across mouse models and brain regions.
• Human Aβ inoculum led to higher Aβ deposition in APP/PS1 cortex compared to Tg2576.
• In Tg2576 mice, human Aβ inoculum resulted in lower Aβ burden than mouse-derived inoculum.

Conclusions:

• Host species influences Aβ strain formation and subsequent pathology.
• Distinct Aβ strains may underlie diverse pathological features in Alzheimer's disease.
• Findings may inform personalized diagnostics and treatments for AD.