HOLES are appearing in the popular idea that insoluble lumps of protein
trigger Alzheimer’s disease. A study of great apes shows that while they do
develop plaques they never get the brain damage associated with dementia.
According to one theory, Alzheimer’s starts when plaques of amyloid protein
accumulate on nerve cells in the brain. These in turn trigger a build-up of
thread-like protein called “tangles” that eventually kill the cells. Patients
can lose up to 60 per cent of the neurons in the entorhinal cortex, a
specialised part of the brain that deals with memory. People who age normally
also develop tangles and lose these cells, but at a far slower rate, says
Patrick Hof of the Mount Sinai School of Medicine in New York.
But when Hof and his colleagues looked at the brains of more than 70
chimpanzees, gorillas and orang-utans, ranging from newborns to 58-year-olds,
they found no tangles and no loss of brain cells due to age in that area. “And
that’s in the presence of a lot of amyloid deposition,” says team member Dan
Perl. This suggests that the plaques may not trigger Alzheimer’s, he says.
Advertisement
These findings support a study in The Lancet last week.
Paul Ince at the Royal Hallamshire Hospital in Sheffield examined the brains of
100 patients who had dementia before they died. He found that a significant
number had few plaques (see “Brain teaser” at www.newscientist.com).
Hof’s study is “powerful and unique”, says James Vickers of the University of
Tasmania in Hobart. But in humans, there seems to be a 5 to 15-year delay
between plaques appearing and brain cell loss. “It may be that the [chimps’]
relatively short lifespan doesn’t give their nerve cells long enough to respond
to the plaques,” he says.
The chimp results are surprising because the animals carry genes that are
associated with Alzheimer’s in humans. All chimps carry two copies of
ApoE4, a variant of a gene that helps repair brains cells. Most humans with
two copies of ApoE4 get Alzheimer’s by the time they are 80 years old.
Chimps also have a variant of a gene called presenilin 1, which is
associated with early-onset Alzheimer’s in humans.
In another study, John Ely of BIOQUAL, a biotech company near Washington DC,
has found subtle differences between the human and chimp versions of the two
genes. “The ultimate hope is that those differences will lead to new therapies,”
he says.
