Alzheimers
and Hope
From www.newscientist.com/section/news
David
Eidensohn
·
Alzheimer one of the great killers
in the world, is at this point without a cure. But is there hope? Here is a news
article with a finding from the BBC of Britain: Home
News
Health
15.3K DAILY NEWS 24
January 2019
We
may finally know what causes Alzheimer’s – and how to stop it
P. gingivalis may be the main culprit in Alzheimer’s disease
A. DOWSETT, PUBLIC
HEALTH ENGLAND/SCIENCE PHOTO LIBRARY
By Debora MacKenzie of BBC News Channel
If you bled when you brushed your teeth this
morning, you might want to get that seen to. We may finally have found the
long-elusive cause of Alzheimer’s disease: Porphyromonas gingivalis,
the key bacteria in chronic gum disease.
That’s bad, as gum disease affects around a
third of all people. But the good news is that a drug that blocks the main
toxins of P. gingivalis is entering
major clinical trials this year, and research published today shows it might
stop and even reverse Alzheimer’s. There could even be a vaccine.
Alzheimer’s is one of the biggest mysteries in medicine. As
populations have aged, dementia has skyrocketed to become the fifth biggest
cause of death worldwide. Alzheimer’s constitutes some 70 per cent of these cases
and yet, we don’t know what causes it.
Bacteria in the brain
The disease often involves the accumulation of proteins called
amyloid and tau in the brain, and the leading hypothesis has been that the
disease arises from defective control of these two proteins.
But research in recent years has revealed that
people can have amyloid plaques without having dementia. So many
efforts to treat Alzheimer’s by moderating these proteins have failed
that the hypothesis has been seriously questioned.
Read more: Here’s how to avoid gum disease
However evidence has been growing that the
function of amyloid proteins may be as a defence against bacteria, leading to a spate of
recent studies looking at bacteria in Alzheimer’s, particularly those that cause gum disease, which is known to
be a major risk factor for the condition.
Bacteria involved in gum disease and other illnesses have been
found after death in the brains of people who had Alzheimer’s, but until now,
it hasn’t been clear whether these bacteria caused the disease or simply got in
via brain damage caused by the condition.
Gum disease link
Multiple research teams have been
investigating P. gingivalis, and have so far
found that it invades and inflames brain regions affected by Alzheimer’s; that gum infections
can worsen symptoms in mice genetically engineered to
have Alzheimer’s; and that it can cause Alzheimer’s-like brain inflammation,
neural damage, and amyloid plaques in healthy mice.
“When science converges from multiple independent laboratories
like this, it is very compelling,” says Casey Lynch of Cortexyme, a
pharmaceutical firm in San Francisco, California.
In the new study, Cortexyme have now reported
finding the toxic enzymes – called gingipains – that P. gingivalis uses to feed on human tissue in 96
per cent of the 54 Alzheimer’s brain samples they looked at, and found the
bacteria themselves in all three Alzheimer’s brains whose DNA they examined.
“This is the first report showing P. gingivalis DNA in human brains, and the
associated gingipains, co-lococalising with plaques,” says Sim Singhrao, of the University of Central Lancashire,
UK. Her team previously found that P. gingivalis actively invades the brains of mice with gum infections.
She adds that the new study is also the first to show that gingipains slice up
tau protein in ways that could allow it to kill neurons, causing dementia.
The bacteria and its enzymes were found at higher levels in
those who had experienced worse cognitive decline, and had more amyloid and tau
accumulations. The team also found the bacteria in the spinal fluid of living
people with Alzheimer’s, suggesting that this technique may provide a
long-sought after method of diagnosing the disease.
When the team gave P. gingivalis gum disease to mice, it led to brain
infection, amyloid production, tangles of tau protein, and neural damage in the
regions and nerves normally affected by Alzheimer’s.
Cortexyme had previously developed molecules that block
gingipains. Giving some of these to mice reduced their infections, halted
amyloid production, lowered brain inflammation and even rescued damaged
neurons.
The team found that an antibiotic that
killed P. gingivalis did this too, but less effectively,
and the bacteria rapidly developed resistance. They did not resist the
gingipain blockers. “This provides hope of treating or preventing Alzheimer’s
disease one day,” says Singhrao.
New treatment hope
Some brain samples from people without
Alzheimer’s also had P. gingivalis and
protein accumulations, but at lower levels. We already know that amyloid and
tau can accumulate in the brain for 10 to 20 years before Alzheimer’s symptoms
begin. This, say the researchers, shows P. gingivalis could
be a cause of Alzheimer’s, but it is not a result.
Gum disease is far more common than Alzheimer’s. But
“Alzheimer’s strikes people who accumulate gingipains and damage in the brain fast
enough to develop symptoms during their lifetimes,” says Lynch. “We believe
this is a universal hypothesis of pathogenesis.”
Cortexyme reported in October that the best of their
gingipain blockers had passed initial safety tests in people, and entered the
brain. It also seemed to improve participants with Alzheimer’s. Later this year
the firm will launch a larger trial of the drug, looking for P. gingivalis in spinal fluid, and cognitive
improvements, before and after.
They also plan to test it against gum disease
itself. Efforts to fight that have led a team in Melbourne to develop a vaccine
for P. gingivalis that started tests in 2018. A vaccine for gum disease
would be welcome – but if it also stops Alzheimer’s the impact could be
enormous.
Journal reference: Science Advances
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