Age is the main risk factor for Alzheimer's disease. But ageing does not necessarily lead to the disease. Nearly 52% of people aged between 70 and 85 complain of cognitive problems, whereas Alzheimer's disease affects only 2 to 8% of people in this age group.
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There are also early forms of the disease, affecting younger people between the ages of 50 and 60. In France, there are currently an estimated 33,000 patients under 60 suffering from Alzheimer’s disease.

Younger patients often present with a different clinical picture to older subjects, with rapid and severe multi-domain cognitive impairment, primarily in memory, but also in attention, language, visuo-spatial and executive deficits. On the other hand, some younger patients may present to their doctor without any primary memory problems. They may, for example, have difficulty finding words or seeing. These are known as focal forms, or language or visuo-spatial variants of Alzheimer’s disease.

There are familial forms of the disease, which are hereditary and caused by extremely rare genetic mutations that account for less than 1% of Alzheimer’s cases. These forms are known as ‘autosomal dominant’, meaning that the mutations are sufficiently severe to trigger the disease in all carrier individuals, usually at a fairly early age.

The vast majority of Alzheimer’s cases are said to be sporadic. Certain environmental factors have now been identified, although a causal relationship has not yet been clearly established. There may also be a genetic predisposition. This can be defined as a combination of genetic variants that confer a greater risk of developing the disease. It is considered that this predisposition alone is not sufficient for the disease to appear, but that it provides a favourable breeding ground for its development.


At the Paris Brain Institute


Lara MIGLIACCO’s group in Richard Lévy’s team is particularly interested in Alzheimer’s disease in young subjects; the so-called focal forms, also known as language variant and visuo-spatial variant of the disease.


Although Alzheimer’s disease is not hereditary (except in 1% of cases), it has been shown that there are genetic predisposing factors, i.e. factors that increase the risk of developing the disease. Previous studies have shown in particular that people carrying a particular allele of the APOE gene, APOEe4, have a risk 3 to 15 times higher than non-carriers, but also that some Alzheimer’s patients do not carry this allele.

On the basis of this knowledge, the “Alzheimer’s disease, prion diseases” team, co-directed by Marie-Claude POTIER, a CNRS researcher at the Institut du Cerveau, hypothesised that a multigenic score could be associated with the future appearance of amyloid plaques in the brain, enabling early targeting of people at greater risk of developing the disease.

The results of this research show an association between the presence of cerebral amyloid plaques and a combination of 17 genetic variants in subjects aged over 70 with no cognitive decline. Assessing the genetic load conferred by these 17 variants, prior to possible detection of amyloid plaques in the brain or plasma, would make it possible to identify very early on those patients most at risk of developing amyloid plaques and thus be able to prevent the onset of the disease through more interventional monitoring.



What are the risk factors 15 years before the first symptoms of Alzheimer’s disease appear? This is a key question for specialists in this neurodegenerative disease, which is known to take more than 10 years to become clinically visible, particularly with a view to improving the early prevention of patients at risk. A multidisciplinary team including researchers from the Aramis project team, led by Stanley Durrleman (Inria) at the Institut du Cerveau (lnserm/CNRS/Sorbonne University), Inserm/University of Bordeaux and Cegedim Health Data, has analysed the anonymised health records of almost 80,000 patients.


Statistical explorations of historical medical records have revealed a list of the 10 most common pathologies encountered by patients who will declare Alzheimer’s disease within 15 years: depression tops the list, followed by anxiety, exposure to severe stress, hearing loss, constipation, cervical spondyloarthritis, memory loss, fatigue (and malaise), and finally falls and sudden weight loss.

It now remains to be determined whether the health problems encountered are risk factors or symptoms or warning signs of the disease.