α-Synuclein modulates tau spreading in mouse brains.

Area of Science:

• Neuroscience
• Neuropathology
• Molecular Biology

Background:

• Alpha-synuclein (α-syn) and tau aggregates are key hallmarks of Parkinson's disease (PD) and Alzheimer's disease (AD).
• Co-occurrence of α-syn and tau pathologies in patients suggests potential crosstalk between these proteins.
• Understanding the interaction between α-syn and tau is crucial for elucidating disease mechanisms.

Purpose of the Study:

• To model and elucidate the interactions between pathological alpha-synuclein and tau.
• To investigate the role of alpha-synuclein in modulating tau pathology.
• To determine if tau influences alpha-synuclein aggregation and spreading.

Main Methods:

• In vitro experiments using alpha-synuclein mouse preformed fibrils (mpffs) and Alzheimer's disease lysate-derived tau seeds (AD-tau).
• In vivo studies utilizing mouse models with and without endogenous alpha-synuclein or tau.
• Assessment of tau aggregate accumulation and spreading following simultaneous introduction of α-syn and tau seeds.

Main Results:

• Simultaneous introduction of α-syn and tau seeds increased tau aggregate accumulation both in vitro and in vivo.
• Absence of endogenous α-syn in mice significantly reduced tau accumulation and spreading.
• Absence of tau did not affect the seeding or spreading capacity of α-syn.

Conclusions:

• Alpha-synuclein plays a critical role in modulating the burden and spread of tau pathology.
• These findings highlight a significant interaction where α-synuclein influences tau pathology in conditions like AD, PD, dementia with Lewy bodies (DLB), and PD dementia (PDD).