Carriers of Alzheimer’s genetic marker have greater difficulty harnessing past knowledge

Summary: Middle-aged people with the Alzheimer’s related APOE4 gene have a harder time accessing recently acquired knowledge, even when they show no symptoms of memory decline.

Source: Baycrest Center for Geriatric Care

Adults carrying a gene associated with a higher risk of Alzheimer’s disease had a harder time accessing recently acquired knowledge, even though they didn’t show any symptoms of memory problems, according to findings published in a joint Baycrest-University of Oxford study.

Researchers found that older adults carrying a specific strain of the gene, apolipoprotein E4, otherwise known as APOE4, weren’t able to tap into information they had just learned to assist them on a listening test.

These findings suggest greater difficulty for these individuals to access knowledge from their memory to guide their attention in ways that would have improved their performance, according to the study published in the journal Scientific Reports. This work could lead to the development of new ways to detect individuals at risk.

The research team worked with 60 research participants (aged 40 to 61) from the Oxford Biobank who had varying combinations of APOE genes – which includes one group of individuals with a combination of APOE3/APOE4 genes, one group of individuals with a set of APOE4 genes and one group of individuals with a set of APOE3 genes. All research participants had normal hearing, scored within the normal range of cognitive assessments and completed a questionnaire about their memory.

Each research participant listened to 92 audio clips and they were told to pay attention to where the clip was coming from, whether it was presented in the left, right or both ears. After the clip was played, they were asked which side they heard the sound from and if they responded incorrectly, the sound was replayed. Participants had a one-hour break before hearing the 92 audio clips again, but this time they were asked whether there was an additional sound at the end of the clip and to press a button when they heard it. Each clip was placed twice. During the first play-through, the clip’s location was replayed and during the second play-through, the additional tone was added.

The study found that no matter the APOE genotype, all older adults were able to learn the information and remember the location of the audio clip, but individuals with the APOE4 gene had greater difficulty in identifying the additional sound at the end of the clip.

This shows two heads
These findings suggest greater difficulty for these individuals to access knowledge from their memory to guide their attention in ways that would have improved their performance. The image is in the public domain.

“For some reason, people with the APOE4 gene were not able to take advantage of information they learned earlier, such as the expected location of the clip, to boost their performance,” says Dr. Claude Alain, a senior author on the paper and senior scientist at Baycrest’s Rotman Research Institute. “This study shows we have a test that is sensitive to capture problems or challenges faced by individuals with this gene, before their deficits are observed on a standard neuropsychological assessment.”

This was an exciting study looking at healthy, middle-aged people who carry a gene that increases their risk of developing Alzheimer’s disease by 15-fold, says Dr. Chris Butler, a senior author on the paper and an associate professor in clinical neurosciences at the University of Oxford.

“The research could lead to more sensitive methods of detecting Alzheimer’s disease in its very earliest stages, the time at which treatments are most likely to be effective,” says Dr. Butler. “I was delighted to carry out this work with researchers from Baycrest.”

As next steps, researchers continue to explore how the brain’s ability to process what is heard changes with neurodegenerative conditions, such as mild cognitive impairment.

Funding: This study was supported by the Medical Research Council and the Weston Brain Institute.

About this neuroscience research article

Baycrest Center for Geriatric Care
Media Contacts:
Josephine Lim – Baycrest Center for Geriatric Care
Image Source:
The image is in the public domain.

Original Research: Open access
“Glucocorticoid exposure during hippocampal neurogenesis primes future stress response by inducing changes in DNA methylation”. Jacqueline Zimmermann, Claude Alain & Chris Butler.
Scientific Reports. doi:10.1038/s41598-019-44471-1


Impaired memory-guided attention in asymptomatic APOE4 carriers

Attention and memory may be impaired in individuals at-risk for Alzheimer’s disease (AD), though standard cognitive assessments typically study the two in parallel. In reality, attention and memory interact to facilitate information processing, and thus a more integrative approach is required. Here, we used a novel auditory paradigm to assess how long-term memory for auditory scenes facilitates detection of an auditory target in asymptomatic carriers of Apolipoprotein E4 (APOE4), the principle risk gene for late-onset AD. We tested 60 healthy middle-aged adults with varying doses of APOE4 – 20 APOE4 homozygotes (E4/E4), 20 heterozygotes (E3/E4) and 20 non-carriers (E3/E3) – to determine effect on memory-guided attention. While explicit memory was unaffected by genotype, APOE4 dose significantly impaired memory-guided attention. A relationship between explicit memory and memory-guided attention was observed in non-carriers, but this correlation was not significant in E3/E4 and E4/E4 carriers, suggesting that APOE4 carriers rely less on explicit memory to facilitate attention. Since memory-guided attention declined with age in APOE4 homozygotes, this impairment may reflect early disease rather than being a life-long trait. In sum, asymptomatic individuals at increased genetic risk of AD show an age-dependent decline in attention-memory interaction when memory alone is not impaired.

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