Alzheimer’s appears far less common in people with a rare genetic mutation

A rare mutation that alters a single letter of the genetic code protects people from the memory-robbing dementia of Alzheimer’s disease, according to a new study. The DNA change may inhibit the buildup of beta-amyloid, the protein fragment that accumulates in the hallmark plaques that form in the brains of Alzheimer’s patients.

Some researchers say the findings are intriguing but not hugely surprising. They fit well, in fact, with current thinking about Alzheimer’s disease.

The newly identified mutation affects a gene called APP, which encodes a protein that gets broken down into pieces, including beta-amyloid. Previously, researchers have identified more than 30 mutations to APP, none of them good. Several of these changes increase beta-amyloid formation and cause an inherited form of Alzheimer’s that afflicts people in their 30s and 40s, much earlier than the far more common late-onset Alzheimer’s.

The new mutation appears to do the opposite. Researchers led by Kari Stefansson at DeCode Genetics in Iceland scanned whole-genome data from 1,795 Icelanders for variations in APP that protect against Alzheimer’s. One variant stood out: a switch of a single nucleotide at one position in the APP gene. Among people 85 or older, those who had this mutation were far less likely to have Alzheimer’s disease than were those who did not have it. Stefansson and colleagues reported the study online last week in the journal Nature.

A naturally occurring variant in a different gene, the APOE2 allele, has been previously shown to protect against Alzheimer’s disease, but Stefansson says the new variant, while rarer, confers much greater protection. It may also protect against memory loss and other cognitive declines even in people who don’t develop Alzheimer’s. When the researchers examined cognitive test results from thousands of people in Icelandic nursing homes, they found that those with the APP mutation tended to fare better through their 80s and 90s than did those without it.

A study shows that a rare mutation in genetic code may protect people from Alzheimer’s disease. (The Washington Post)

— Adapted from ScienceNOW, the online daily news service of the journal Science