Alzheimer’s Disease Progression Predicted by Gene Mutation

It is a degenerative condition, characterized by a steady loss of memory and a reduced ability to carry out daily activities. Today, an estimated five million people in the USA are living with the disease.

The hallmark of Alzheimer's disease is a buildup of two types of protein: beta-amyloid plaques outside of nerve cells, and tau tangles within neurons. Although these proteins appear to be involved in the pathology of Alzheimer's, little is known about why the condition begins and how it progresses. Early detection is still difficult, and treatment options are poor.

Scientists at University of Wisconsin School of Medicine and their colleagues enrolled 1,023 adults, baseline age 54.94 ± 6.41 years, all were healthy but at risk of developing Alzheimer's. They were followed for a maximum of 13 years. At the start of the study, blood samples were taken to test for genotyping and cognitive assessment at up to five time points. Also, 140 of them underwent neuroimaging to look for beta-amyloid plaques.

The team examined the influence of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on longitudinal cognitive trajectories in a large, cognitively healthy cohort enriched for Alzheimer disease (AD) risk and to understand whether β-amyloid (Aβ) burden plays a moderating role in this relationship. The Met allele mutation was found to be present in 32% of the individual, and compared to BDNF Val/Val homozygotes, Met carriers showed steeper decline in verbal learning and memory and speed and flexibility. In addition, Aβ burden moderated the relationship between BDNF and verbal learning and memory such that Met carriers with greater Aβ burden showed even steeper cognitive decline.

Ozioma Okonkwo, PhD, the lead author of the study, said, “The current treatment is most successful if given earlier in the disease's progression, this could be a vital part of the jigsaw. Because this gene can be detected before the symptoms of Alzheimer's start, and because this presymptomatic phase is thought to be a critical period for treatments that could delay or prevent the disease, it could be a great target for early treatments.” The study was published on May 3, 2017, in the journal Neurology.