Neuroscientists at the Massachusetts Institute of Technology (MIT) have found that rare variants of the ABCA7 gene may increase the likelihood of developing Alzheimer's disease. The results of the study are published in the journal Nature.

The ABCA7 gene is responsible for transporting lipids (fats) across cell membranes. Lipid metabolism disorders have previously been linked to another known risk factor for Alzheimer's disease — a variant of the APOE4 gene, which is found in almost half of all patients. Previous studies have shown that APOE4 impairs the ability of brain cells to process fats and resist stress.

To study the role of ABCA7, scientists analyzed 1,200 tissue samples from elderly people. The researchers identified 12 that belonged to carriers of rare variants of ABCA7. 

RNA sequencing of individual cells showed that the absence of normal ABCA7 affects the function of genes associated with lipid metabolism, DNA damage repair, and energy metabolism (oxidative phosphorylation).

To test these findings, the scientists introduced ABCA7 variants into neurons grown from stem cells. The results confirmed that in such cells, mitochondrial function was impaired and their ability to limit the accumulation of electrical charge was reduced, leading to excessive oxidative stress and tissue damage.

In addition to rare mutations, researchers studied a more common variant of ABCA7, found in approximately 18% of people. It was previously considered safe, but experiments have shown that even in this case, changes in lipid metabolism similar to those seen in rare mutations are observed.