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A simple test could distinguish who will go on to develop Alzheimer’s

A simple test that detects hyperactivity of a brain region which plays a vital role in memory could be enough to determine if the patient will develop the Alzheimer’s disease and therefore receive treatment before first symptoms appear.

Oxford researcherThis is the main conclusion of a research carried out by the University of Oxford and the Imperial College of London, in which it has been compared the brain activity of 36 volunteers aged between 20 and 35, half of them with gene ApoE4, related with this disease.

The research, published in the journal Proceedings of the National Academy of Sciences, provides clues as to why certain people develop Alzheimer’s disease and it may be a step towards a diagnostic test that identifies individuals at risk. The degenerative condition is the most common cause of dementia and it affects around 417,000 people in the UK.

The ApoE4 genetic variant is found in about a quarter of the population. Not everyone who carries the variant will go on the develop Alzheimer’s, but people who inherit one copy of ApoE4 have up to four times the normal risk of developing the late-onset variety of the disease. People who have two copies have around ten times the normal risk.

The researchers behind the study stress that most carriers of ApoE4 will not go on to develop Alzheimer’s and carriers should not be alarmed by the study’s findings.

HippocampusDifferences in the region of the brain involved in memory, known as the hippocampus, have previously been shown in middle-aged and elderly healthy carriers of ApoE4. The hippocampus is the area of the brain responsible for forming memories and for spatial orientation. In Alzheimer’s disease, the hippocampus is one of the first areas of the brain to be damaged, and its effects are seen early in Alzheimer’s by disorientation of the patient.

However, the new Oxford University and Imperial study is the first to show hyperactivity in the hippocampus of healthy young carriers. It is also the first to show that ApoE4 carriers’ brains behave different even at ‘rest’.

The study used functional Magnetic Resonance Imaging (fMRI) carried out at the University of Oxford to compare activity inside the brains of the 36 volunteers, with 18 carrying at least one copy of the ApoE4 gene and 18 non-carriers acting as controls.

The researchers looked at how the volunteers’ brains behaved while they were resting and also while they were performing a memory-related task. Even when the ApoE4 carriers were resting, the researchers could see that carriers and non-carriers each had distinct patterns of brain activity. The fMRI scans showed visible differences in how the hippocampus was relating to the rest of the brain.

Alzheimer's brain scanning‘We have shown that brain activity is different in people with this version of the gene decades before any memory problems might develop’, Dr Clare Mackay, the lead author of the study from the Department of Psychiatry and the Centre for Functional Magnetic Resonance Imaging of the Brain at the University of Oxford, said. ‘We’ve also shown that this form of fMRI, where people just lie in the scanner doing nothing, is sensitive enough to pick up these changes. These are exciting first steps towards a tantalising prospect: a simple test that will be able to distinguish who will go on to develop Alzheimer’s’, Dr Mackay pointed too.

Dr Christian Beckmann, another author of the study from the Division of Neurosciences and Mental Health at the Imperial College of London, added: ‘We’re very surprised of seeing that even when volunteers who carry the gene didn’t do anything, the part of their brain related with memory worked harder than the rest of volunteers. Not all the ApoE4 carriers go on to develop Alzheimer’s, but it would make sense if in some people, the memory part of the brain effectively becomes exhausted form overwork and this contributes to the disease. This theory is supported by studies that have found the opposite pattern in people who have developed Alzheimer’s, with these people showing less activity than normal in the memory part of the brain’.


COGKNOW is funded by the European Comission within the IST-2005/2006-2.5.11 (Unit H3 - eInclusion) Contract #034025

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