New study characterizes cognitive and anatomic differences in Alzheimer's disease gene carriers

May 17, 2010

In the most comprehensive study to date, neurologists have clearly identified significant differences in the ways that Alzheimer's disease (AD) affects patients with and without the apolipoprotein E ε4 gene (APOE ε4), a known genetic risk factor for the neurodegenerative disease, using a combination of cognitive and neuroanatomic measures. The study found that this gene influences the way the disease manifests, even at its mildest clinical stages.

Study highlights include:

  • Patients with mild AD who carry the ε4 form of the APOE gene perform more poorly on memory tests and have more prominent abnormalities in critical for memory, compared with patients without this gene variant.
  • In contrast, patients with mild AD who do not have the APOE ε4 gene perform more poorly on tests of attention, language, and executive function and have more prominent abnormalities in brain regions critical for these abilities, compared to patients with APOE ε4.
"These findings have important implications for how we diagnose, treat and follow patients with ," said David Wolk, MD, assistant professor of Neurology at the Penn Memory Center and lead author on the study. "Genetic factors, like the APOE gene, seem to result in somewhat different patterns of cognitive impairment - the degree to which memory or attention is affected - and the brain regions vulnerable to the disease process."

Both APOE ε4 carriers and non-carriers displayed impaired memory in the study, but in qualitatively different ways. Researchers note that a variety of types of cognitive tests - tasks looking at memory, language, attention, and executive function - are necessary to make an early diagnosis and monitor of the progression of AD effectively. So far, the emphasis for early diagnosis and monitoring of AD has largely been on memory tests.

The study appears in the latest issue of the Proceedings of the National Academy of Sciences (PNAS).

Using data collected from the Alzheimer's Disease Neuroimaging Initiative, a large multi-center North American study of possible biomarkers for AD, neurologists from the Penn Center at the University of Pennsylvania School of Medicine and the Massachusetts Alzheimer's Disease Research Center at Massachusetts General Hospital (MGH) and Harvard Medical School(HMS) examined how the presence or absence of the ε4 form of APOE influences cognitive function and brain anatomy measured from MRI scans.

Studying participants diagnosed with mild AD, the researchers compared the differences in cognition and in regional cortical atrophy of 67 APOE ε4 carriers with those of 24 non-carriers. Results from a biomarker test of cerebral spinal fluid, developed and previously reported by Penn Medicine researchers, was used to confirm with high diagnostic accuracy that patients included in the study had a molecular profile consistent with AD.

For future clinical trials, the researchers note that APOE genotype should be considered when analyzing the effects of possible treatments.

"A few recent clinical trials reported differences in the way patients responded to the drugs being tested depending on whether or not they carried the ε4 allele, which have prompted groups to study these populations independently," said senior author Bradford C. Dickerson, MD, associate professor of Neurology at MGH and HMS. "Rather than restricting trials exclusively to patients with or without APOE ε4, the results from this paper suggest that different behavioral and brain measures, dependent on participants' genotype, might be a useful approach to consider in evaluating investigational drugs."

Ultimately, a personalized medicine approach may factor an individual's genetic status in when considering how to diagnose and monitor the disease.

Related Stories

Recommended for you

Urine test developed to test for tuberculosis

December 14, 2017
(Medical Xpress)—An international team of researchers has developed a urine test that can be used to detect tuberculosis (TB) in human patients. In their paper published in Science Translational Medicine, the group describes ...

40 years after first Ebola outbreak, survivors show signs they can stave off new infection

December 14, 2017
Survivors of the first known Ebola outbreak, which occurred in the Democratic Republic of the Congo in 1976, may be key to development of vaccines and therapeutic drugs to treat future outbreaks, according to a new study ...

Lactic acid bacteria can protect against Influenza A virus, study finds

December 13, 2017
Lactic acid bacteria, commonly used as probiotics to improve digestive health, can offer protection against different subtypes of influenza A virus, resulting in reduced weight loss after virus infection and lower amounts ...

Lyme bacteria survive 28-day course of antibiotics months after infection

December 13, 2017
Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the US, today announced results of two papers published in the peer-reviewed journals PLOS ONE and American Journal of Pathology, that seem to support ...

Aging impairs innate immune response to flu

December 13, 2017
Aging impairs the immune system's response to the flu virus in multiple ways, weakening resistance in older adults, according to a Yale study. The research reveals why older people are at increased risk of illness and death ...

Drug blocks Zika, other mosquito-borne viruses in cell cultures

December 12, 2017
If there was a Mafia crime family of the virus world, it might be flaviviruses.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.