New approach to Alzheimer’s ‘a scalpel instead of a sledgehammer’

New research by the the University of British Columbia could lead to an Alzheimer’s treatment that gives patients ‘many more years of life’ before cognitive decline sets in.

Scientists had previously identified crucial steps in the formation of a protein called amyloid beta, which accumulates in clumps in the brains of people with Alzheimer’s disease.

Those discoveries inspired efforts at disrupting the biochemical carving of amyloid beta’s precursor protein into its final, toxic shape.

The latest drugs being tested try to silence an enzyme, called BACE1, that cuts the precursor protein. But BACE1 has other functions that are beneficial, so stopping it altogether could bring unwanted side effects.

Alzheimer’s researcher Weihong Song found that changing where the cut is made could achieve the same goal, with less collateral damage.

Song built upon two discoveries in the past decade of two rare mutations: one found in Italian people that leads to early onset Alzheimer’s disease, and another found in Icelandic people that staves off the condition.

The researchers injected one set of mice with a virus carrying the Italian gene mutation, and another set with the Icelandic mutation.

They found that the amino acid substitution affected where the precursor protein was cleaved. The Icelandic mutation resulted in a shortened form of amyloid beta, which does not turn into plaque. The Italian mutation produced a longer version of amyloid beta, which ultimately becomes neuron-smothering plaque.

The researchers say that reducing the levels of the toxin could translate into ‘many more years of life’ before cognitive decline sets in.

Dr. Song, the study’s lead author, said: ‘If we can adjust where BACE1 cuts the precursor protein, we will have a very precise way of slowing the build-up of plaque in the brain, without affecting other processes. This provides a new target in our search for a drug – instead of sledgehammer, it’s more like a scalpel.’

Instant analysis

Finding an effective treatment for Alzheimer’s disease remains the Holy Grail of modern medicine. This is unlikely to be one major break through but instead a combination of small discoveries and this study will add to that knowledge.

It is known that the accumulation of a protein called amyloid beta in the brain triggers Alzheimer’s and so anything that stops or slows this will impact on the disease progressing. Scientists at the University of British Columbia followed on from the discovery that a rare genetic mutation in some Icelandic people seemed to stave off the condition.

Using studies in mice they showed that by genetically altering the action of an enzyme called BACE 1 – which affects the development of protein plaques in the brains of patients – they may be able to slow the build up of amyloid and so increase the length of time before patients experience cognitive decline. A small study to be sure, and much more work is needed in this area, but this is another positive step towards a treatment for Alzheimer’s.

Research score: 3/5

RH