A New Way to Detect Alzheimer's Disease

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APOE is the main genetic risk factor for this disease, but that is not the whole story; Xabier Elcoroaristizabal is looking for complementary genetic factors
One of our genes is apolipoprotein E (APOE), which often appears with a variation which nobody would want to have: APOEε4, the main genetic risk factor for sporadic Alzheimer’s disease (the most common form in which this disorder manifests itself and which is caused by a combination of hereditary and environmental factors). It is estimated that at least 40% of the sporadic patients affected by this disease are carriers of APOEε4, but this also means that much more still remains to be studied. The researcher at the University of the Basque Country (UPV/EHU) Xabier Elcoroaristizabal has opened up a channel for making a start by analysing candidate genes which, always in combination with APOEε4, could help to explain more cases. His thesis is entitled “Molecular markers in mild amnestic cognitive impairment and Alzheimer’s disease” (Marcadores moleculares en deterioro cognitivo leve tipo amnésico y enfermedad de Alzheimer). An initial article on this can be read in the journal BMC Neuroscience.

The long-term aim is to contribute towards the early detection of Alzheimer’s disease by identifying signs that could be detectable in the very early phases. And, as Elcoroaristizabal explains, while there is no cure for this disorder, the alternative is to get ahead of it and delay its development: “Certain preventive measures involving cognitive stimulation delay its appearance. There are even new drugs that could start to be used earlier. Today there is no solution, but the more we maintain a person’s correct cognitive state, the better.”

Mild amnestic, cognitive impairment

The individuals who develop Alzheimer’s go through a transition period first of all, and this could be the key moment for the effective application of preventive measures. This is mild cognitive impairment (MCI), in which slight cognitive alterations take place but do not affect everyday activities. Among the different types of MCI, one affects memory almost exclusively (amnestic MCI), and those people who suffer from it have a high probability of developing the disorder. The difficult and interesting part is knowing which genetic components are linked to this impairment and also in determining by what percentage the risk of developing the disease increases, a task which Elcoroaristizabal has set himself. “If we can identify which genes are involved and what susceptibility factors there are, preventive measures could be taken,” he explains.

So a contrast study has been carried out among a sample of patients with MCI, ones with Alzheimer’s and healthy people. This can be used to observe the changes and narrow down the field for the zones to be studied, so that candidate genes can be sought there. Elcoroaristizabal himself notes one example among the many others identified: “It has been observed that the brain's capacity to control cholesterol levels seems to play a key role throughout the illness. So, protein encoding genes linked to this control have been analysed.”

In this quest for candidate genes, Elcoroaristizabal has confirmed that the APOEε4 genetic variation is, in fact, the main risk factor for developing Alzheimer’s disease. But it does not end there; he has identified several genes which, as long as they are manifested in combination with APOEε4, could take us one step further towards the early detection of this disorder. “Genes that in some way are connected with neurotransmission channels, oxidative stress or the effectiveness of oestrogens seem to be linked to a greater risk for APOEε4 carriers,” he explains. Specifically, the candidate genes are as follows: COMT (neurotransmission), SOD2 (oxidative stress elimination) and ESR1 and ESR2 (oestrogen action facilitators).