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Is Alzheimer's a Form of
Diabetes?
By Catherine Guthrie
When the body refuses to
make insulin, the
condition is called type
1 diabetes; when
the body mismanages the
hormone, it's known as
type 2. Now, scientists
report new
evidence linking insulin
to a disorder of the
brain: when the brain
prevents the
hormone from acting
properly, the ensuing
chemical imbalance may
help trigger
Alzheimer's disease. The
correlation is so strong
that some researchers
are calling
Alzheimer's disease
"type 3" diabetes.
In the body, insulin
helps convert food into
cellular energy. But the
brain has other
uses for insulin, namely
as a means to learn and
make new memories.
Here's how it
works: At synapses, the
spaces across which
brain cells communicate
and where
memories are conceived,
neurons reserve special
parking spots just for
insulin. When
the hormone pulls in, a
connection is made that
enables new memories to
form.
Since new memory
formation is one of the
first things to go awry
in people with early
stages of the disease,
this insulin-initiated
process may hold the key
to decoding the
mystery of Alzheimer's.
In August, a team of
scientists at
Northwestern University
were the first to show
why
the brain's "memory
function" fails in the
face of an insulin
shortage. The group's
prior research had
already pinpointed the
culprit: toxic proteins
called amyloid
betaderived
diffusible ligands (ADDLs,
for short), which are
known to pile up in the
brains of people with
Alzheimer's. Scientists
also knew that
Alzheimer's patients'
brains have lower levels
of insulin and are
insulin resistant. But
what the
Northwestern team
discovered is the
molecular mechanism
behind that resistance:
when ADDLs bind to
neurons at synapses,
they obliterate the
receptors that are
normally reserved for
insulin. Without those
parking spaces on the
brain cells'
surface, insulin has no
place to connect, and
memory fails.
"We now understand that
the function of insulin
at those synapses is to
modulate
and influence the
underlying cellular
structure of memories,"
says William Klein,
professor of
neurobiology and
physiology at
Northwestern University
and a coauthor
of the study published
online by the FASEB
Journal. "What we have
here is a
striking phenomenon that
may ultimately explain
why the brains of people
with
Alzheimer's disease are
insulin resistant and
how that ties into
memory."
Researchers hope these
findings will help shape
future research in
Alzheimer's
therapy — perhaps in the
development of drugs
that can make brain
cells' insulin
receptors more
responsive to the
hormone, or in the
application of type 2
diabetes
drugs, which address
insulin resistance, to
Alzheimer's.
The notion that
Alzheimer's disease
might be a
neuroendocrine disorder,
akin to
diabetes, isn't entirely
new; it first showed up
in the scientific
literature roughly 20
years ago, but the idea
petered out. In 2005,
Suzanne la Monte, a
neuropathologist at
Brown University Medical
School, revisited the
idea. Based on two of
her discoveries
— that the brain makes
its own insulin and that
Alzheimer's disease
depletes insulin
— she coined the disease
process "type 3"
diabetes.
Still, referring to
Alzheimer's disease as
"type 3" diabetes is
controversial,
especially
within the diabetes
community. Alzheimer's
disease is a
complication of
diabetes, not
a unique form of the
disease, says Dr. Sue
Kirkman, vice president
of clinical affairs
for the American
Diabetes Association.
"Nevertheless," she
says, "this is primarily
a
semantic argument."
The terminology aside,
both diseases share many
traits and risk factors,
including
high cholesterol, high
blood pressure, and
metabolic disorders. So,
de la Monte sees
the semantic "splitting
of hairs" as a good
thing. "People are
arguing about small
parts of the bigger
story," she says. "At
the end of the day,
these conversations will
help us to better
understand both diabetes
and Alzheimer's
disease."
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