Novel gene variant shows protective effect against Alzheimer's disease

Researchers at the University Medical Centre Hamburg-Eppendorf (UKE) have identified a gene variant in an international study that could protect against Alzheimer's disease. Together with scientists from Harvard Medical School, the University of Antioquia/Colombia and other institutions, they were able to determine that a variant of the so-called reelin gene regulates cell biological processes that contribute to the development of Alzheimer's disease. The findings could represent a new starting point in Alzheimer's therapy. The researchers have published the results of their study in the journal Nature Medicine.

The researchers were able to determine an unusual disease progression for this genetic form of Alzheimer's in a carrier of the so-called Paisa mutation in Colombia: The patient developed mild dementia at the age of 72 and died at the age of 74 - decades after most people with this mutation typically develop dementia. Genetic tests showed that the patient carried a novel, rare variant of the reelin gene. Reelin is a protein that plays a central role in regulating the development and function of brain cells. In further studies led by the UKE, the researchers discovered that this reelin gene variant protects against the destruction of brain cells by counteracting a central mechanism in the development of Alzheimer's - the deposition of the so-called tau protein in nerve cells. This protective effect was also particularly strong in the entorhinal cortex, a key region of the brain for learning processes and memory, whose nerve cells are usually the first to be damaged in the course of Alzheimer's disease.

„The protective gene variant described in this study opens up a new perspective on the reelin protein and the development of Alzheimer's disease The fact that a gene has a protective effect against the development of Alzheimer's disease may form an important basis for future therapeutic studies,

says Dr Diego Sepulveda-Fallao. Diego Sepulveda-Falla from the Institute of Neuropathology at the UKE.

The scientists have published the results of their study in the journal Nature Medicine. In 2019, a similar case of the disease from the same population was investigated. Here, a genetic variant in a different protein was identified that was responsible for the slower progression of the disease. Both cases nevertheless point to a similar disease mechanism in the entorhinal cortex.

Source: Press release Universitätsklinikum Hamburg-Eppendorf from 15 May 2023