- 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
- Alzheimer's disease is a progressive neurodegenerative disorder
characterized by memory loss, behavioral and motor problems, and is the
most common form of dementia
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.
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
"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.
the Polygenic Hazard Testing Tool
The new test measures the combined effects of over two dozen gene
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
‘Multiple gene testing identifies individuals with other genetic combinations that might increase Alzheimer’s disease risk although they may be APOE E4 gene negative’
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
- 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.
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.
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 (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
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.
- 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/)
- Alzheimer's disease - (https://en.wikipedia.org/wiki/Alzheimer%27s_disease)
- What Is Alzheimer's? - (http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp)