Delta-secretase triggers Alzheimer’s disease pathologies in wild-type hAPP/hMAPT double transgenic mice

Cell Death & Disease, 2020 · DOI: 10.1038/s41419-020-03270-7 · Published: December 11, 2020

Simple Explanation

This research investigates Alzheimer's disease (AD) pathologies using a novel mouse model with human wild-type APP and Tau. The study demonstrates that δ-secretase, an enzyme, can trigger AD-like pathologies in these mice, even without any AD-related mutations. Overexpression of δ-secretase accelerates the formation of senile plaques and neurofibrillary tangles (NFTs), leading to cognitive deficits.

Study Duration

3 Months

Participants

Mice

Evidence Level

Not specified

Key Findings

1
hAPP/hMAPT double-transgenic mice, carrying both human wild-type APP and Tau, exhibit AD-related pathologies.
2
Overexpression of δ-secretase in hAPP/hMAPT mice accelerates senile plaque and NFT formation, associated with synaptic defects and cognitive decline.
3
δ-secretase overexpression leads to increased Aβ production, neuroinflammation, and neuronal loss in the hAPP/hMAPT mice.

Research Summary

The study demonstrates that δ-secretase is sufficient to promote prominent AD pathologies in wild-type hAPP/hMAPT double transgenic mice. Overexpression of δ-secretase in these mice accelerated the formation of senile plaques and NFTs, leading to cognitive dysfunction. This research provides insight into the molecular mechanisms of sporadic AD pathogenesis, independent of patient-derived mutations.

Practical Implications

Therapeutic Target

δ-secretase could be a potential therapeutic target for treating Alzheimer's disease.

Sporadic AD Understanding

The study sheds light on the mechanisms driving sporadic AD cases, which lack genetic mutations.

New Animal Model

The hAPP/hMAPT double-transgenic mice provide a valuable new model for studying AD pathogenesis.

Study Limitations

1
The study is limited to a mouse model, and findings may not directly translate to humans.
2
The exact mechanisms by which δ-secretase initiates AD pathogenesis require further investigation.
3
The long-term effects of δ-secretase overexpression were not fully explored.

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