Novel Mutations Linked to Early-onset Alzheimer’s Found in Asian Countries

Researchers reviewed the novel mutations found in genes associated with early-onset Alzheimer’s disease in Asian countries, arguing that identifying disease-associated mutations greatly contributes to the knowledge of the cause and effect of the disease. This information is also essential to develop preventive and therapeutic strategies.

The study, “Mutations, Associated With Early-Onset Alzheimer’s Disease, Discovered In Asian Countries,” was published in the journal of Clinical Interventions in Aging. 

Alzheimer’s disease can be classified into the early-onset and late-onset types. The early-onset form is more rare and hereditary, developing before the age of 65. Essentially, three genes are known to be involved in this form of the disease: APP, PSEN1, and PSEN2.

APP encodes the amyloid precursor protein which, when cleaved, will become the beta-amyloid protein, whose toxic accumulation is the hallmark of Alzheimer’s. The other two genes, PSEN1 and PSEN2, encode proteins that cleave the amyloid precursor protein, contributing to the formation of the beta-amyloid protein. Mutations in these three genes may promote beta-amyloid production and accumulation.

Here, researchers reviewed all of the known mutations in these three genes that were discovered in Asian countries, such as Japan, Korea, and China. According to the authors, 30 novel Asian mutations were found in APP, PSEN1, and PSEN2 comparing Caucasian and Asian patients.

Most mutations associated with early-onset Alzheimer’s have been detected in PSEN1, and novel PSEN1 mutations were recently identified in patients from various parts of the world, including Asia. Other studies discovered what were probably pathogenic PSEN2 mutations in Korea and China.

“Several mutations were discovered in APP, PSEN1, and PSEN2 that could contribute to disease progression,” the authors wrote. “Most of these mutations are associated with familial [early-onset Alzheimer’s]. However, several [new] cases of [Alzheimer’s] were reported in patients without any family history of dementia.”

“The majority of pathogenic mutations were found in PSEN1 gene,” they added. “Several PSEN1 mutations could be associated with early-onset [Alzheimer’s], which occurs at the age of 40 years, and with rapid and aggressive dementia progression. Mutations in APP and PSEN2 are quite rare but are possible causative factors [for early-onset disease]. Pathogenic mutations could result in disease onset at the age of 40-65 years.”

Although there is no known cure for Alzheimer’s disease, potential therapeutic approaches might be successful in early stages of the disease. The problem is that diagnosing the disease before clinical symptoms occur is complicated.

The identification of proteins and genes that can act as biomarkers for disease onset is essential to improve diagnosis, especially given that several genes have already been described as causative or risk factor genes for dementia.

For this reason, knowing which mutations are associated with Alzheimer’s disease may become a powerful strategy to predict the development of this disease before the appearance of symptoms, and allow the start of prevention therapies in patients.