48 | New Scientist | 6 November 2021
bacteria that cause gum disease. A study of
nearly 30,000 people suggested that having
severe gum disease for at least 10 years
increased the risk of developing Alzheimer’s
by about 70 per cent. In 2019, researchers at
US biopharmaceutical company Cortexyme
published findings on a specific gum disease
bacterium called Porphyromonas gingivalis.
They found this microbe – as well as the toxic
enzymes it produces – in the brains of people
with Alzheimer’s after they had died. In mice,
they showed that this bacterium could migrate
from the mouth to the brain. Giving the mice
a drug that blocks the activity of the toxic
enzymes reduced inflammation in the brain
and lowered levels of one type of beta-amyloid.
The company has now recruited more than
600 people with mild to moderate Alzheimer’s
disease for a clinical trial of the drug. Results
are expected by the end of 2021.
As for how to reduce your risk: there isn’t
yet a direct link between dental hygiene and
Alzheimer’s risk, but it is probably a good idea
to brush, floss and see your dentist regularly.Friendly fire?
It may not be the microbes themselves causing
Alzheimer’s, but rather how our bodies
respond to them and other perceived threats.
Multiple studies have indicated that infection
with herpes viruses can trigger beta-amyloid
accumulation, for example. Initially at least,
this response may protect the brain: Tanzi,
along with colleagues Robert Moir and Richard
Lathe, has hypothesised that amyloid is
actually an antimicrobial protein that sticks to
and neutralises viruses or bacteria that get into
the brain. At first, amyloid triggers an immune
response – inflammation – which helps to clear
the infection. But if inflammation persists,
it can cause harm. One aspect of this
inflammatory response is that brain cells
known as microglia and astrocytes become
activated into a neuron-damaging state,
“housekeepers turned killers”, says Tanzi.
He and others are trying to find a way to flip
the switch back. “We’ve been screening every
approved drug, every natural product, for the
ability to tell microglial cells and astrocytes to
stop killing and go back to work as nurturers
and housekeepers for the neurons,” he says.So far, they have about 35 promising substances.
The next step is to test these in animals.
But taming microglia is just one way to
reduce inflammation, which can be triggered
in many ways. We know, for instance, that
people with autoimmune disorders such as
rheumatoid arthritis or Crohn’s disease have
higher levels of a pro-inflammatory protein
called tumour necrosis factor (TNF). Malú
Tansey, director of the Center for Translational
Research in Neurodegenerative Disease at the
University of Florida, says that people with
long-term elevated levels of TNF have a higher
risk of developing neurodegenerative disease,
but that anti-TNF therapies can reduce this.
In mouse models of Alzheimer’s, Tansey and
her colleagues have shown that blocking TNF
helps improve neuronal function.
Tansey says build-up of proteins like beta-
amyloid is important for Alzheimer’s, but
doesn’t believe it is the initiating factor. “We
need to think about protein aggregation not
as triggering the inflammatory immune
dysfunction, but resulting from it,” she says. By
identifying and treating immune dysfunction,
we may be able to prevent the disease.Several studies have confirmed that
there is a risk of covid-19 having
neurological and psychiatric
complications, such as anxiety,
depression and delirium. More recently,
we have begun to uncover worrying
connections between coronavirus
infection and Alzheimer’s-like
symptoms in some people. Gabriel de
Erausquin at the University of Texas
Health Science Center at San Antonio is
conducting a study on older people who
tested positive for the virus. “What we
found is that a remarkable number of
people over 60 years of age that have
been exposed to the virus – compared
with people who remained PCR-
negative – have cognitive impairment.
It’s close to 60 per cent,” he says.
De Erausquin says this is about
10 times more than he would have
expected in a group of this age. He says
that while many people primarily had
forgetfulness, others had more severe
impairment, including problems with
attention and language. While some
of the people in this study ended up
in hospital with covid-19, most didn’t,
and initial severity of symptoms
wasn’t related to the severity of later
problems with cognition.
Other research presented at the
recent Alzheimer’s Association
International Conference in Colorado
analysed blood biomarkers in people
with covid-19 who ended up in hospital,
with and without neurological
symptoms. Those with certain
neurological symptoms had elevated
levels of biomarkers related to
Alzheimer’s disease and neuronal
damage, including tau and a protein
called neurofilament light chain.
While it is possible that the changes
de Erausquin and others have observed
are the beginnings of Alzheimer’s, it is
also possible that these individuals will
recover. We simply don’t have enough
information yet. Right now, says de
Erausquin, “the crucial experiment is
to figure out what is the course of this”.Covid-19 and
cognition