Basic Science and Pathogenesis

Area of Science:

• Neuroscience
• Pathology
• Biochemistry

Background:

• Alzheimer's disease (AD) involves amyloid-β plaques and tau tangles.
• Tau pathology may spread systemically, but its impact on AD is unclear.
• Peripheral tau aggregates are found in tissues and fluids, with unknown effects on brain pathology.

Purpose of the Study:

• To investigate if peripheral tau aggregates contribute to Alzheimer's disease (AD) progression.
• To analyze tau distribution and brain infiltration after systemic administration.
• To assess the interaction between peripheral and central tau dynamics.

Main Methods:

• Blood from tauopathy mice was administered to P301S transgenic mice.
• Intravenous (i.v.) and intraperitoneal (i.p.) routes were used for administration.
• Behavioral, biochemical, and histological analyses assessed tau aggregation and brain pathology.

Main Results:

• Injection of blood-borne tau aggregates exacerbated tau pathology in the brain.
• Evidence suggests an interaction between peripheral and central tau dynamics.
• Peripheral tau aggregates may contribute to disease progression.

Conclusions:

• Peripheral tau aggregates can act as pathological seeds, potentially driving AD progression.
• Understanding systemic tau dissemination offers insights into AD pathogenesis.
• This research may identify novel biomarkers and therapeutic targets for neurodegenerative diseases.