Biomarker test
confirming or ruling out Alzheimer's
validated
Newswise — A test capable of confirming or
ruling out Alzheimer’s disease has been
validated and standardized by researchers at
the University of Pennsylvania School of
Medicine.
By measuring cerebrospinal fluid (CSF)
concentrations of two of the disease’s
biochemical hallmarks – amyloid beta42
peptide and tau protein – the test also
predicted whether a person’s mild cognitive
impairment would convert to Alzheimer’s
disease over time.
Researchers were able to detect this
devastating disease at the earliest stages,
before dementia symptoms appeared and
widespread irreversible damage occurred.
The findings hold promise in the search for
effective pharmaceutical therapies capable
of halting the disease.
Homing in on a previously suggested
pathological CSF biomarker signature, a team
of Penn Medicine researchers, led by Leslie
M. Shaw, PhD, Co-Director of the Penn
Alzheimer’s Disease Neuroimaging Initiative
(ADNI) Biomarker Core, found evidence of
neuron degeneration – marked by an increase
in CSF concentration of tau proteins – and
plaque deposition, indicated by a decrease
in amyloid beta42 concentration.
In addition, people with two copies of the
genetic risk factor for Alzheimer’s disease,
APOE ε4 , had the lowest concentrations of
amyloid beta42, compared to those with one
or no copies. The study appears in the
online edition of the Annals of Neurology.
“With this test, we can reliably detect and
track the progression of Alzheimer’s
disease,” said Dr. Shaw.
“Validated biomarker tests will improve the
focus of Alzheimer’s clinical trials,
enrolling patients at earlier stages of the
disease to find treatments that can at least
delay –and perhaps stop– neurodegeneration.
“In addition, prevention trials can test
methods to delay or block mild cognitive
impairment from converting to full-blown
Alzheimer’s.”
Further validation studies of this research
test system are underway. Additional work is
needed to develop additional biomarkers, as
well as identify more genetic risk factors
that will help distinguish Alzheimer’s from
other neurodegenerative diseases
characterized by cognitive impairments.
“Thanks to the dedicated researchers and
volunteers who participated in this and
other Alzheimer’s disease studies through
the Penn Alzheimer’s Disease Core Center and
at ADNI trial sites around the US and
Canada, we have validated a test where a
safe, simple lumbar puncture can provide
information to confirm suspected Alzheimer’s
disease and predict the onset of the
disease,” said John Q. Trojanowski, MD, PhD,
Director of the Penn Alzheimer’s Disease
Core Center.
“Using this technique, we will further our
understanding of how the disease progresses
and what we can do to stop Alzheimer’s
disease before it starts.”
About the Study
Cerebral spinal fluid samples contributed by
410 ADNI volunteers at 56 sites across the
U.S. and Canada were included in this study.
To independently establish threshold values
for these biomarkers, cerebrospinal fluid
samples from 52 Penn Memory Center
volunteers with normal cognition and 56
people with confirmed Alzheimer’s disease
based on post-mortem autopsy diagnosis were
also measured.
The test was based on the multiplexed xMAP
microbead immunoassay system, with reagents
provided by Innogenetics.
When compared with normal, healthy adults of
the same age, a pattern of changes emerged
in people with mild cognitive impairment or
Alzheimer’s disease. In this group, tau
concentrations increased, while amyloid
beta42 levels decreased as the disease
progressed.
• The test was 87 percent accurate overall
(80 percent or above is considered
clinically useful).
o In the CSF samples from those with
autopsy-confirmed Alzheimer’s disease, the
amyloid beta42 concentration threshold was
most sensitive and detected Alzheimer’s
disease at a rate of 96.4 percent.
o The test accurately ruled out Alzheimer’s
disease in 95.2 percent of the subjects.
o The test positively predicted the
conversion from mild cognitive impairment to
Alzheimer’s disease at a rate of 81.8
percent.
