Rare genetic mutation protective against Alzheimer's disease

A rare genetic
mutation, found in about one percent of Icelanders in a recent study, appears to protect against Alzheimer's disease and age-related cognitive decline. It
is the first mutation found to act in this way and could be a target
for future drug therapy.

The mutation is
located in the amyloid-beta precursor protein (APP) gene and prevents the gene's product from forming the
protein plaques that are typical of Alzheimer's disease.

Amyloid-beta plaques
have long been the suspected cause of Alzheimer's disease, although researchers
lack conclusive evidence; the plaques could in fact be a
consequence of other biochemical changes associated with the disease. This
study provides strong support that amyloid-beta plaques are the real
culprits.

'If amyloid-beta
plaques were confirmed as the cause of Alzheimer's, it would bolster efforts to
develop drugs that block their formation in order to treat or prevent the
ravaging condition', reports an article in Nature News, paraphrasing Dr Kari Stefansson,
chief executive of deCODE Genetics in Reykjavik, Iceland, who led the research.

Dr Stefansson added
that the study indicated 'that Alzheimer's, and the cognitive decline that
awaits all of us if we survive long enough, seems to be mediated through the
same mechanism'.

The mutation leads to
a slightly different form of APP being produced. The altered section of this APP
variant sits next to the site where enzymes split APP into the amyloid-beta proteins
that form Alzheimer's plaques. The researchers think the mutation makes it more
difficult for the cleaving enzymes, called BACE enzymes, to find the cleavage
site.

'We've found the
first protective mutation in Alzheimer's disease and provided proof of concept
for using BACE inhibitors to treat the disease', Dr Stefansson told the
Guardian. 'So if big pharma manages to develop an effective BACE inhibitor, it
should probably be put into the drinking water of elderly people'.

Dr Stefansson said that he plans to use his company's platform to investigate
rare mutations relevant to other diseases such as ovarian cancer and gout next.
'The rare variants are not going to explain a large amount [of disease], but
they are going to provide very key mechanistic insights into how all of this
happens', he told Nature News.