[Alzheimer’s might not be primarily a brain disease. Studying
beta-amyloids as abnormal proteins that cause Alzheimer’s disease
has not translated into a useful drug or therapy. A new theory
suggests it’s an autoimmune condition. ]
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ALZHEIMER’S DISEASE: CONTROVERSY, SCANDALS AND NEW THEORIES  
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Donald Weaver
September 19, 2022
The Conversation
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_ Alzheimer’s might not be primarily a brain disease. Studying
beta-amyloids as abnormal proteins that cause Alzheimer’s disease
has not translated into a useful drug or therapy. A new theory
suggests it’s an autoimmune condition. _

PET scan of an healthy brain compared to a brain at an early stage of
Alzheimer's disease" , by Institut Douglas, licensed under CC BY-NC-ND
2.0

 

The pursuit of a cure for Alzheimer’s disease is becoming an
increasingly competitive and contentious quest with recent years
witnessing several important controversies.

In July 2022, _Science_ magazine
[[link removed]]
reported that a key 2006 research paper, published in the prestigious
journal _Nature_ [[link removed]], which
identified a subtype of brain protein called beta-amyloid as the cause
of Alzheimer’s, may have been based on fabricated data.

One year earlier, in June 2021, the U.S. Food and Drug Administration
had approved aducanumab
[[link removed]],
an antibody-targeting beta-amyloid, as a treatment for Alzheimer’s,
even though the data supporting its use were incomplete and
contradictory. Some physicians believe aducanumab never should have
been approved, while others maintain it should be given a chance.

With millions of people needing an effective treatment, why are
researchers still fumbling in this quest for a cure for what is
arguably one of the most important diseases confronting humankind?

Escaping the beta-amyloid rut

For years, scientists have been focused on trying to come up with new
treatments for Alzheimer’s by preventing the formation of
brain-damaging clumps of this mysterious protein
[[link removed]] called beta-amyloid.
In fact, we scientists have arguably got ourselves into a bit of an
intellectual rut concentrating almost exclusively on this approach,
often neglecting or even ignoring other possible explanations.

[Illustration showing red clusters of amyloid plaques in brain tissue]

Studying beta-amyloids as abnormal proteins that cause Alzheimer’s
disease has not translated into a useful drug or therapy. Shutterstock

Regrettably, this dedication to studying the abnormal protein clumps
has not translated into a useful drug or therapy. The need for a new
“out-of-the-clump” way of thinking about Alzheimer’s is emerging
as a top priority in brain science.

My laboratory at the Krembil Brain Institute, part of the University
Health Network in Toronto, is devising a new theory of Alzheimer’s
disease [[link removed]]. Based on our past 30
years of research, we no longer think of Alzheimer’s as primarily a
disease of the brain. Rather, we believe that Alzheimer’s is
principally a disorder of the immune system within the brain
[[link removed]].

The immune system, found in every organ in the body, is a collection
of cells and molecules that work in harmony to help repair injuries
and protect from foreign invaders. When a person trips and falls, the
immune system helps to mend the damaged tissues. When someone
experiences a viral or bacterial infection, the immune system helps in
the fight against these microbial invaders.

The exact same processes are present in the brain. When there is head
trauma, the brain’s immune system kicks into gear to help repair.
When bacteria are present in the brain, the immune system is there to
fight back.

Alzheimer’s as autoimmune disease

We believe that beta-amyloid is not an abnormally produced protein,
but rather is a normally occurring molecule that is part of the
brain’s immune system. It is supposed to be there. When brain trauma
occurs or when bacteria are present in the brain, beta-amyloid is a
key contributor to the brain’s comprehensive immune response. And
this is where the problem begins.

Because of striking similarities between the fat molecules that make
up both the membranes of bacteria and the membranes of brain cells,
beta-amyloid cannot tell the difference between invading bacteria and
host brain cells, and mistakenly attacks the very brain cells it is
supposed to be protecting.

This leads to a chronic, progressive loss of brain cell function,
which ultimately culminates in dementia — all because our body’s
immune system cannot differentiate between bacteria and brain cells.

[Close-up view of a section of a human brain]

A section of a human brain with Alzheimer’s disease displayed at the
Museum of Neuroanatomy at the University at Buffalo, in Buffalo, N.Y.
(AP Photo/David Duprey)

When regarded as a misdirected attack by the brain’s immune system
on the very organ it is supposed to be defending, Alzheimer’s
disease emerges as an autoimmune disease. There are many types of
autoimmune diseases, such as rheumatoid arthritis, in which
autoantibodies play a crucial role in the development of the disease,
and for which steroid-based therapies can be effective. But these
therapies will not work against Alzheimer’s disease.

The brain is a very special and distinctive organ, recognized as the
most complex structure in the universe
[[link removed]]. In our model of
Alzheimer’s, beta-amyloid helps to protect and bolster our immune
system, but unfortunately, it also plays a central role in the
autoimmune process that, we believe, may lead to the development of
Alzheimer’s.

Though drugs conventionally used in the treatment of autoimmune
diseases may not work against Alzheimer’s, we strongly believe that
targeting other immune-regulating pathways in the brain will lead us
to new and effective treatment approaches for the disease.

Other theories of the disease

[A drawing of a brain inside a yellow light bulb, against a green
background.]

It is gratifying to see new thinking about this age-old disease.
(Pixabay)

In addition to this autoimmune theory of Alzheimer’s, many other new
and varied theories are beginning to appear. For example, some
scientists believe that Alzheimer’s is a disease of tiny cellular
structures called mitochondria
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in every brain cell. Mitochondria convert oxygen from the air we
breathe and glucose from the food we eat into the energy required for
remembering and thinking.

Some maintain that it is the end-result of a particular brain
infection [[link removed]], with bacteria
from the mouth often being suggested as the culprit
[[link removed]]. Still others suggest that the
disease may arise from an abnormal handling of metals within the brain
[[link removed]], possibly zinc, copper or iron.

It is gratifying to see new thinking about this age-old disease
[[link removed]]. Dementia currently
affects more than 50 million people worldwide, with a new diagnosis
being made every three seconds. Often, people living with
Alzheimer’s disease are unable to recognize their own children or
even their spouse of more than 50 years.

Alzheimer’s is a public health crisis in need of innovative ideas
and fresh directions. For the well-being of the people and families
living with dementia, and for the socioeconomic impact on our already
stressed health-care system coping with the ever-escalating costs and
demands of dementia, we need a better understanding of Alzheimer’s,
its causes, and what we can do to treat it and to help the people and
families who are living with it.[The Conversation]

Donald Weaver
[[link removed]], Professor
of Chemistry and Director of Krembil Research Institute, University
Health Network, _University of Toronto
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This article is republished from The Conversation
[[link removed]] under a Creative Commons license. Read
the original article
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* Science
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* Medicine
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* alzheimer's
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* drug industry
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* FDA
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