Predicting Alzheimer’s Disease Risk – Multiple Gene Testing Better Than APOE Gene Testing Alone

Highlights :

• A multiple gene testing tool that predicts more accurately, could be beneficial to identify the risk of developing Alzheimer’s disease compared to apolipoprotein E E4 (APOE E4) gene testing alone

• Alzheimer’s disease is a progressive neurodegenerative disorder characterized by memory loss, behavioral and motor problems, and is the most common form of dementia

Multiple gene testing can better identify individuals at risk of developing Alzheimer’s disease compared to testing only the APOE E4 gene as is usually done currently, according to a team of scientists at UC San Francisco and UC San Diego. The findings of the study appear in the journal Annals of Neurology in September 2017.

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How Multiple Gene Testing is Superior to APOE E4 Testing Alone

For a long time, APOE E4 gene has been linked to increased risk of Alzheimer’s disease although only 15 percent of the population carry this variant. The study team feel that there are other gene variants and/or combination of gene variants occurring in the remaining 85 percent, which may also be associated with an increased Alzheimer’s disease risk. They opine that the significance of APOE E2 gene may have been overstated. "Beyond APOE E4 by itself, our polygenic hazard score can identify cognitively normal and mildly impaired older folks who are at greatest risk for developing Alzheimer's-associated clinical decline over time," said Chin Hong Tan, PhD, a postdoctoral scholar at UCSF and first author of the paper.

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Testing the Polygenic Hazard Testing Tool

The new test measures the combined effects of over two dozen gene variants including APOE E4. Each of these, by itself singly, is associated with only a slight risk of Alzheimer’s disease. However, the presence of multiple gene variants in combination is able to more accurately predict the risk of Alzheimer’s dementia.

The team analyzed the data on 1081 individuals from the National Alzheimer's Coordinating Center (NACC) who did not have dementia. The notable observations were as follows

• The polygenic hazard scoring (PHS) test predicted how long it would take to progress to Alzheimer's dementia.

• Additionally, the test was able to correctly predict how steep the mental decline would be, after taking into account whether they were APOE E4 gene carriers.

In persons who did develop Alzheimer’s disease, the important revelations were as follows

• Persons who were not APOE E4 carriers but showed a high PHS score were found to have higher levels of amyloid aggregates in their brains.

• The rate of cognitive decline had been higher during the life in those persons who showed a high PHS score.

• Older individuals falling in the highest PHS percentiles displayed the highest incidence of Alzheimer's, diagnosed by means cognitive tests and brain pathology, inspite of what their APOE E4 status was.

"Our findings have strong implications for disease stratification and secondary prevention trials in Alzheimer's, as well as direct-to-consumer genetic tests, some of which have recently received FDA clearance," said Anders Dale, PhD, Professor of Neurosciences and Radiology at UC San Diego and co-author of the new study.

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What is the Polygenic Hazard Score (PHS) Test?

The PHS test employs genetic data from over 70,000 people in the NACC database, the International Genomics of Alzheimer's Disease Project and the Alzheimer's Disease Genetics Consortium to predict Alzheimer’s disease. Using these known data, the PHS test helps scientists in calculating age-specific risk of developing Alzheimer's, based upon each person's share of 31 genetic variants including APOE E4.

Scope of the PHS Test

The PHS testing has been developed using known data on Alzheimer’s disease and may thus emerge as a reliable marker to predict Alzheimer’s disease risk in normal adults so that appropriate interventions could be instituted.

"Unlike other polygenic risk scores, the continuous PHS measure is based on a survival framework and incorporates US-based Alzheimer's incidence rates," said Rahul Desikan, MD, PhD, an assistant professor in the Department of Radiology and Biomedical Imaging at UCSF, and co-senior author of the paper. "Rather than a diagnostic test, PHS may serve as a genetic 'risk factor' for preclinical Alzheimer's disease."

Alzheimer’s Disease (AD) – in Brief

Alzheimer’s disease is the most common form of dementia, usually affecting persons 65 years or older. It is a progressive neurodegenerative disorder marked by severe memory loss and cognitive impairments severe enough to affect daily routine activities and make them increasingly dependent on others.

Currently nearly 30 million persons worldwide suffer from Alzheimer’s disease and it has been estimated to be the seventh leading cause of death in the US. The cause of AD is poorly understood and there is no cure although medications can control the symptoms and reduce progression.

The current study is one of several research projects going on worldwide on Alzheimer’s disease aiming to throw light on this enigmatic condition and giving hope to individuals suffering from this debilitating condition.

References:

1. From Brain Disease to Brain Health: Primary Prevention of Alzheimer’s Disease and Related Disorders in a Health System Using an Electronic Medical Record-Based Approach - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573186/)
2. Alzheimer's disease - (https://en.wikipedia.org/wiki/Alzheimer%27s_disease)
3. What Is Alzheimer's? - (http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp)

Source-Medindia