Genetic variant protective against Alzheimer’s has beneficial effects on amyloid-beta metabolism

1 / 1sAPPβ and Aβ42 levels are significantly reduced in CSF samples of APP A673T variant carriers as compared to controls. Peptide levels were measured with ELISA from CSF samples. Levels of sAPPα and sAPPβ were normalized to sAPPtot (total levels of soluble APP α+β). Data are shown as mean +SD of n=3 individuals. Credit: DOI: 10.1016/j.nbd.2023.106140

A new study conducted by researchers at the University of Eastern Finland discovered that the APP A673T genetic variant, which protects against Alzheimer’s disease, alters levels of several proteins and peptides linked to amyloid-beta metabolism in human biofluids and cell culture models, including amyloid beta itself. These new data support the idea that even a modest reduction in the beta-amyloidogenic processing of APP may be a feasible strategy for the prevention of Alzheimer’s disease. Alzheimer’s disease (AD) is the most common form of dementia with more than 40 million affected people worldwide. Two of the key pathological features of AD are amyloid plaques, composed of toxic amyloid-beta (Aβ) peptides, and neurofibrillary tangles, consisting of hyperphosphorylated tau protein. Although these molecular characteristics have been known for decades, there have been many setbacks in the development of therapies for an effective prevention or treatment of AD. However, recent clinical trials targeting different steps of Aβ aggregation have shown promise in slowing down the disease progression. Aβ is part of the amyloid precursor protein (APP) and it is generated upon the sequential proteolytic cleavage of APP.

By  University of Eastern Finland

Article can be accessed on: MedicalXpress