New test may predict onset of Alzheimer’s

Los Angeles, March 22
A new test that allows individuals to calculate their age-specific risk of Alzheimer’s disease based on their genetic information has been developed by researchers including one of Indian origin.
Researchers from University of California, San Francisco (UCSF)in the US found that polygenic hazard score (PHS) strongly predicted empirical age of Alzheimer’s disease (AD) onset and progression from normal ageing to AD, with strongly associated neuropathology and biomarkers of AD neurodegeneration.
They combined genotype-derived polygenic information with known AD incidence rates to derive instantaneous risk estimates for developing AD.
“We combined genetic data from large, independent cohorts of patients with AD with epidemiological estimates to create the scoring, then replicated our findings on an independent sample and validated them with known biomarkers of Alzheimer’s pathology,” said Rahul S Desikan of UCSF.
“For any given individual, for a given age and genetic information, we can calculate your ‘personalised’ annualised risk for developing AD,” said Desikan.
“That is, if you don’t already have dementia, what is your yearly risk for AD onset, based on your age and genetic information.
“We think these measures of polygenetic risk, of involving multiple genes, will be very informative for early AD diagnosis, both in determining prognosis and as an enrichment strategy in clinical trials,” Desikan added.
Researchers analysed genotype data from more than 70,000 AD patients and normal elderly controls.
They then scrutinised 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.
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.
They developed a continuous 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.
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 study was published in the journal PLOS Medicine.