New research shows that the APP gene variant protecting against Alzheimer’s disease significantly decreases plasma beta-amyloid levels in a population cohort. This is a significant discovery because many ongoing drug trials in the field of Alzheimer’s disease focus on decreasing beta-amyloid levels in the brain tissue. According to the study, a 30% life-long decrease in beta-amyloid levels is not associated with detrimental effects on lipid or glucose metabolism, or on any other metabolic factors.

The findings were published in Annals of Neurology.

Alzheimer’s disease is a neurodegenerative disease strongly characterised by the accumulation of beta-amyloid in the brain tissue. Uncovering the genetic pathogenesis of Alzheimer’s disease has been a target of great interest over the past few years, and genome-wide mapping studies focusing on risk genes have led to significant advances in the field. These studies have identified not only several new risk genes for Alzheimer’s disease, but also gene variants that protect against it.

Research groups focusing on Alzheimer’s disease and diabetes have now shown that the APP A673T gene variant, which is a variant in the amyloid precursor protein gene protecting against Alzheimer’s disease, leads to an average of 30 per cent decreased levels of the beta-amyloid subtypes 40 and 42. The effects of this previously discovered gene variant were analysed by utilising data from the unique and extensive METSIM study, which comprises 10,000 men living in the eastern part of Finland. Approximately 0.3% of the population are carriers of the APP A673T gene variant.

The findings on the role of the APP A673T gene variant in Alzheimer’s disease facilitate the planning of future research. This insight, in turn, could enable the identification of new drug targets, increasingly good predictive biomarkers and the development of personalised medical applications.

Paper: “Decreased plasma β-amyloid in the Alzheimer’s disease APP A673T variant carriers”
Reprinted from materials provided by University of Eastern Finland.

September 4, 2017