Alzheimer-disposition compromises the brain’s ‘GPS’ in young adults

Alzheimer's patients suffer from severe memory loss and disorientation. An international research team now shows that a genetically increased risk for Alzheimer’s disease affects a brain region known as ‘the brain’s GPS’ in healthy young adults. Christian Doeller from Radboud University’s Donders Institute is one of leaders of the study, together with Nikolai Axmacher from Ruhr-Universität Bochum. Their results were published in Science on October 22.

Alzheimer's disease is caused by an interaction of factors, among others a certain variant of the APOE gene: one in six people carries this variant and has a three-fold increased risk to develop Alzheimer's disease.

Navigating in an MRI scanner

In their study, Doeller, Axmacher and colleagues investigated groups of young adults with and without the critical APOE risk gene. The participants navigated through a virtual environment while lying in an MRI scanner. At the same time, the researchers looked at the activity in their entorhinal cortex: the brain area that is first affected by Alzheimer’s disease and that contains so called ‘grid cells’ that play an important role in navigation; hence the term ‘GPS of the brain’.

A less stable GPS

‘People with the risk gene showed a less stable activity pattern in the entorhinal cortex, even decades before the possible onset of the disease,’ says researcher Tobias Navarro-Schröder from the Donders Institute. ‘In addition, their brain activity was increased as a whole in the memory system, which could in the short term compensate for the reduced activity in the entorhinal cortex, but in the long term contribute to the development of Alzheimer's disease.’

New navigation strategy

Furthermore, participants with the risk gene were less frequently moving in the middle of the virtual landscape, suggesting a change in navigation strategy. They tended to stay at the edge of the landscape, as this is a more clear navigation point than the middle. Still, all participants scored roughly the same for the task in the MRI scanner, showing that the new navigation strategy eventually led to the same end result.

Project leader Christian Doeller summarizes: ‘These findings contribute to a better understanding of early changes in Alzheimer's disease. Now we need to test whether similar changes also occur in older people with early Alzheimer's disease and whether they can be influenced by drugs.

You can find more information about this publication on the website of the Doeller Lab at Radboud University’s Donders Institute:

Reduced grid-cell-like representations in adults at genetic risk for Alzheimer’s disease
Kunz L, Navarro Schröder T, Lee H, Montag C, Lachmann B, Sariyska R, Reuter M, Stirnberg R, Stöcker T, Messing-Floeter PC, Fell J, Doeller CF*, Axmacher N* (2015). (*shared senior author)

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