Alzheimer’s amyloid protein development halted in mice

30 Apr

Promising results from a new mouse study suggest there may be a way to halt the

formation of a faulty protein that clogs up the brain in people with Alzheimer’s


woman with dementia and carer
The researchers believe if the findings translate to humans, the new compounds could stop Alzheimer’s disease in its tracks.

Writing in the journal PLOS ONE, researchers from the University of

California-San Diego (UCSD) School of Medicine and Cenna Biosciences, Inc. describe how

they identified compounds that block the production of beta-amyloid peptides in mice.

The team suggests if the findings translate to humans, then the most promising of the

new compounds – which they refer to as P8 – could be given to people at high risk of

developing Alzheimer’s disease long before the signs of dementia appear.

Lead author Nazneen Dewji, an associate adjunct professor in the Department of

Medicine at UCSD, says:

“We are blocking the actual production of beta-amyloid in a new way. It’s very

promising because it means that, in principle, we can stop the disease in its


She and her colleagues believe it is likely the new drug would have few side effects because of how it acts specifically on one target – amyloid precursor protein (APP).

New compounds specifically target APP

Exactly what causes the brain to waste away in Alzheimer’s disease is not clear, but

scientists believe the abnormal amounts of faulty proteins in the form of amyloid plaques

and tau tangles found in the brains of people who have died with the disease have

something to do with it.

The malformed proteins interfere with the effective working of brain cells, resulting

in the host of cognitive and movement impairments that are associated with Alzheimer’s

disease, which accounts for up to 80% of all cases of dementia in the US.

The researchers explain that other experimental drugs that tackle amyloid proteins

target the enzymes that cleave beta-amyloid from its larger precursor protein APP.

But those experimental compounds have largely failed in trials, Prof. Dewji says,

“mostly because they are responsible for cleaving other proteins besides APP. Inhibiting

or modifying their activities creates many undesirable effects in the cell.”

The P8 compound in this new study does not act on enzymes – it binds to APP and blocks

the process that cuts it up into the smaller amyloid peptides.

P8 and the other related compounds that the team has developed are made from a

fragment of a membrane protein called presenilin 1 that is known to interact with APP to

produce beta-amyloid.

The team was able to show how well P8 bound only to APP using both biophysical methods

and optical imaging techniques.

2-week treatment led to 50% reduction in amyloid plaques in mice

Prof. Dewji – who is also president and CEO of Cenna, the biopharmaceutical company in

La Jolla, CA, where the compounds are being developed – explains:

“Our approach is different, specific and interferes with only the reaction

that produces beta-amyloid, as opposed to drugs that target the enzymes responsible for

its cleavage from APP, which can affect multiple reactions in cells.”

For their study, she and her colleagues carried out experiments in cell culture and

mice engineered to produce large amounts of the human beta-amyloid early in life.

They found that on average, compared with untreated mice, the treated ones

showed a 50% or more reduction in amyloid plaque accumulation following a 2-week course with

either P8 or another of the candidate compounds, P4.

Prof. Dewji concludes:

“We now have a new approach for the treatment of Alzheimer’s disease that can arrest

the production of beta-amyloid very early and specifically. It’s a real chance at a

successful treatment for Alzheimer’s disease.”

Meanwhile, Medical News Today recently learned about another study where scientists

found a potential cause of Alzheimer’s disease in the immune system. There,

a team from Duke University in Durham, NC, found that in the early stages of Alzheimer’s,

some immune cells that normally protect the brain begin instead to chew up arginine, an

important amino acid.