Ideally, a blood-based screening test would identify
people who have started down the path toward
Alzheimer’s years before they could be diagnosed
based on symptoms.
Decades before people with Alzheimer’s disease
develop memory loss and confusion, their brains
become dotted with plaques made of a sticky protein
called amyloid beta that is thought to contribute to
the disease and its progression.
Currently, the only way to detect amyloid beta in
the brain is via PET scanning, which is expensive
and not widely available, or a spinal tap, which is
invasive and requires a specialized medical
“Our results demonstrate that this amyloid beta
blood test can detect if amyloid has begun
accumulating in the brain,” said Randall J. Bateman,
MD, the Charles F. and Joanne Knight Distinguished
Professor of Neurology and the study’s senior
“This is exciting because it could be the basis for
a rapid and inexpensive blood screening test to
identify people at high risk of developing
As the brain engages in daily tasks, it continually
produces and clears away amyloid beta.
Some is washed into the blood, and some floats in
the cerebrospinal fluid, for example.
If amyloid starts building up, though, it can
collect into plaques that stick to neurons,
triggering neurological damage.
A blood test would be cheaper and less invasive than
PET scans or spinal taps, but previous studies have
found that measures of total levels of amyloid beta
in the blood don’t correlate with levels in the
So Bateman and colleagues measured blood levels of
three amyloid subtypes – amyloid beta 38, amyloid
beta 40 and amyloid beta 42 — using highly precise
measurement by mass spectrometry to see if any
correlated with levels of amyloid in the brain.
The researchers studied 41 people ages 60 and older.
Twenty-three were amyloid-positive, meaning they had
signs of cognitive impairment.
PET scans or spinal taps in these patients also had
detected the presence of amyloid plaques in the
brain or amyloid alterations in the cerebrospinal
The researchers also measured amyloid subtypes in 18
people who had no buildup of amyloid in the brain.
To measure amyloid levels, production and clearance
over time, the researchers drew 20 blood samples
from each person over a 24-hour period.
They found that levels of amyloid beta 42 relative
to amyloid beta 40 were consistently 10 to 15
percent lower in the people with amyloid plaques.
“Amyloid plaques are composed primarily of amyloid
beta 42, so this probably means that it is being
deposited in the brain before moving into the
bloodstream,” Bateman said.
“The differences are not big, but they are highly
consistent,” he explained.
“Our method is very sensitive, and particularly when
you have many repeated samples as in this study —
more than 500 samples overall — we can be highly
confident that the difference is real. Even a single
sample can distinguish who has amyloid plaques.”
By averaging the ratio of amyloid beta 42 to amyloid
beta 40 over each individual’s 20 samples, the
researchers could classify people accurately as
amyloid-positive or -negative 89 percent of the
On average, any single time point was also about 86
Amyloid plaques are one of the two characteristic
signs of Alzheimer’s disease; the other sign is the
presence of tangles of a brain protein known as tau.
David Holtzman, MD, the Andrew B. and Gretchen P.
Jones Professor and head of the Department of
Neurology at the School of Medicine, is developing a
blood-based test for tau that could complement the
“If we had a blood test for tau as well, we could
combine them to get an even better idea of who is
most at risk of developing Alzheimer’s disease,”
Bateman said. “That would be a huge step forward in
our ability to predict, and maybe even prevent,
Study of noninvasive retinal imaging device
presented at Alzheimer's conference (2014-07-14)
Alzheimer's Association: know the 10 signs, early
detection matters (2016-02-23)
For more information
Amyloid ß concentrations and stable isotope labeling
kinetics of human plasma specific to central nervous
Washington University School of Medicine