Researchers from Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, and three other teams discovered the Shanghai APP mutation in a Chinese patient who developed memory loss in his mid-70s.
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Exploring the therapeutic implications of the Shanghai APP mutation
Neuroimaging methods confirmed its existence widespread amyloid £]deposition, It is the main symptom of AD. Using molecular dynamics simulations and in vitro experiments, the team found that the E674Q mutation causes increased processing of APP and production of amyloid £]a toxic protein associated with AD.
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In addition, biochemical aggregation experiments showed that The E674Q peptide showed higher aggregation than the wild-type peptide, especially the formation of filaments connecting several fibrils.
To further investigate the in vivo effects of the mutation, the researchers introduced the E674Q mutant APP gene into the hippocampi of two-month-old mice using adeno-associated virus (AAV) gene transfer.
As a result of the research, it was found that The E674Q mutation resulted in impaired learning behavior and increased pathological burden in a mouse model, demonstrating a pathogenic role in AD.
The E674Q substitution exhibited a strong amyloidogenic effect and, to the researchers’ knowledge, is the only known pathogenic mutation within the amyloid processing sequence to cause LOADS.
From Discovery to Hope
This finding is important because it may open new ways to understand the development of AD and lead to more effective treatments for patients suffering from this form of Alzheimer’s disease.
The new discovery of the Shanghai APP mutation provides a unique opportunity to further investigate the molecular mechanisms underlying DOWNLOAD.
Further studies on the effects of the E674Q mutation are important to explore the potential development of targeted therapies or interventions. Slowing or stopping the progression of AD.
By understanding how this specific mutation contributes to the initiation and progression of LOAD, scientists can develop new strategies to prevent or treat this devastating disease, ultimately improving the quality of life for tens of millions of patients and their families.
Reference:
- E674Q (Shanghai APP mutant), a novel amyloid precursor protein mutation in familial late-onset Alzheimer’s disease – (https://www.sciencedirect.com/science/article/pii/S2352304223001277)
Source: Eurekalert
