Reacción a "A single copy of a protective gene variant helps delay early Alzheimer's disease"

Just a month ago a study of thousands of people was published showing that those with two copies of the E4 allele of the apolipoprotein E gene (APOE) had a form of Alzheimer's disease that behaved like another genetic form. These two copies led to poor brain function leading to dementia at ages not as advanced as in the general population.  

Today we come across a study that analyses a single family of Colombian origin in which, in addition to a genetic variant causing AD in the Presenilin 1 gene (PSEN1), some individuals also have a very rare allele in the APOE gene called Christchurch (APOE3^Ch). This work shows that, in this family, individuals with variants in PSEN1 and APOE3^Ch have Alzheimer's disease that appears a few years later than in their relatives who only have the PSEN1 variant. This delay in the age of onset is also accompanied by fewer lesions in the brain, including vascular lesions, which were more abundant in carriers of the PSEN1 variant. 

A few years ago, this same group observed how a member of this family carried two copies of this allele, APOE3^Ch, and despite also having the PSEN1 variant that caused AD in his relatives at around 40 years of age, he showed no signs of dementia in his late 70s. That finding is now extended by the demonstration that a single copy of APOE3^Ch may be moderately beneficial and joins another recent paper from another group showing that this variant may be beneficial in that astrocytes possessing it are more resistant to the spread of tau lesions than those without this variant.  

Taken together, these findings have a very important aspect that was not so clear a short time ago: there are ways to slow the progression of Alzheimer's disease. Although the authors restrict the effect of this variant in APOE to the Colombian family, the evidence presented by other authors, for example, the work mentioned above, allows us to foresee that the moderate effect of the APOE3^Ch variant may occur in the general population. 

Deciphering the mechanisms that make a person moderately resistant to the progression of Alzheimer's disease may lead to the identification of new mechanisms that could lead to effective therapies. In fact, the fact that a single genetic variant possesses this ability may mean that slowing down the disease, although not simple, may be achievable.