An international team of scientists has developed a novel genetic score that allows individuals to calculate their age-specific risk of developing Alzheimer’s disease (AD) based upon genetic information.

A description of the polygenic hazard scoring (PHS) system and its validation were published in PLOS Medicine.

The researchers combined genotype-derived polygenic information with known AD incidence rates from the U.S. population to derive instantaneous risk estimates for developing AD.

To conduct the study, the research team analyzed genotype data from more than 70,000 AD patients and normal elderly controls who were participating in several projects, such as the Alzheimer’s Disease Genetics Consortium, the National Alzheimer’s Coordinating Center and the Alzheimer’s Disease Neuroimaging Initiative. The team scrutinized the data for AD-associated single nucleotide polymorphisms (SNPs), which are variations of a single nucleotide or DNA building block that occur at a specific position in the genome. There is some SNP variation in genomic information in all humans, which affects individual susceptibility to disease. In this case, the researchers looked at SNPs linked to AD risk and for APOE status. Persons with the E4 variant in the APOE gene are known to be at greater risk of developing late-onset AD.

The researchers developed a continuous polygenic hazard score or PHS based upon this data to predict age-specific risk of developing AD, then tested it in two independent cohorts or defined groups of people. They found persons in the top PHS quartile developed AD at a considerably lower age and had the highest yearly AD incidence rate. Importantly, PHS also identified people who were cognitively normal at baseline but eventually developed AD. Even among people who did not have the APOE E4 allele, the most important genetic risk factor for AD, PHS informed age of onset; individuals with high PHS scores developed AD 10-15 years earlier than individuals with low PHS.

The authors found that PHS strongly predicted empirical age of AD onset and progression from normal aging to AD, with strongly associated neuropathology and biomarkers of AD neurodegeneration.

Paper “Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score”
Reprinted from materials provided by University of California San Diego

3 Απριλίου, 2017