Scientific American Mind - USA (2020-03 & 2020-04)

according to the study, published in
Science Translational Medicine.
Essentially, beta-amyloid hijacks
the norepinephrine pathway to
trigger a toxic buildup of tau, says
Qin Wang, the study’s senior author
and a professor of neuropharmacolo-
gy in the department of cell, develop-
mental and integrative biology at the
University of Alabama at Birming-
ham. “We really show that this
norepinephrine is a missing piece
of this whole Alzheimer’s disease
puzzle,” she says.
This cascade explains why so many
previous Alzheimer’s treatments have
failed, Wang says. Most of the drugs
developed in recent decades have
targeted the elimination of beta-amy-
loid. But the new research suggests
that norepinephrine amplifies the
damage wrought by that protein.
Beta-amyloid itself can kill neurons
but only in very high doses, Wang
says. Add norepinephrine, and it takes
only 1 to 2 percent as much beta-am-
yloid to eliminate brain cells in a lab
dish. So with treatments that targeted
beta-amyloid but left the norepineph-
rine pathway intact, there was enough
beta-amyloid remaining to do signifi-
cant damage, she says. But if the
norepinephrine pathway really is

crucial to the development of Alzhei-

mer’s, it suggests new ways to treat

the disease, which currently afflicts

5.8 million Americans.

A drug that was developed to treat

depression but was too ineffective to

win approval seems to act on this

same pathway, Wang says. The drug,

idazoxan, which has also been studied

in schizophrenia, has already passed

through initial clinical testing and

been shown to be safe, she adds.

Wang is now looking to promote

larger clinical trials of idazoxan to see

if it can be used to effectively treat

early-stage Alzheimer’s. She hopes

that eventually, a drug can be devel-

oped that will act on this Alzhei-

mer’s-related pathway in a more

targeted way to minimize side effects

and maximize effectiveness.

Stephen Salloway, a professor of

psychiatry and neurology at the

Warren Alpert Medical School at

Brown University, who was not

involved in the new research, says he

doesn’t think Alzheimer’s will yield so

easily to a new drug targeting the

norepinephrine pathway. “I doubt

there’s something simple that’s going

to come out of this,” says Salloway,

who is also director of neurology and

the Memory and Aging Program at

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