A post-mortem diagnosis is all very well in criminal investigation,
but it doesn't do much for the living. Alzheimer's disease
(AD) is, famously, the disease that can only be categorically
diagnosed when you're dead. The amyloid plaques blamed
for killing brain cells in Alzheimer's patients often
don't show up on scans, so a functioning diagnosis generally
depends on cognitive tests. Unfortunately, if the results
are clear, it means the damage has already been done.
So it's no surprise that the announcement of a possible
test for early Alzheimer's made a few headlines.
Using a new technique called bio-barcode
amplification (BCA), scientists found a marker that's
consistently elevated in the cerebrospinal fluids of
patients previously diagnosed with Alzheimer's, and
consistently low in healthy age-matched controls.
The markers are proteins called
ADDLs, short for amyloid ß-derived diffusible
ligands. A recent theory argues that ADDLs accumulate
at the beginning of Alzheimer's disease and block memory
function. The theory also predicts that this process
could be reversible if caught early enough.
The 'bio-barcode' test is performed
by injecting microscopic particles with four components
- an ADDL antibody, a magnetic nanoparticle, a gold
nanoparticle, and hundreds of strands of DNA. In the
cerebrospinal fluid, the antibodies bind to ADDLs, altering
the DNA. The magnetic quality of the particles makes
it easy to 'vacuum' them up from cerebrospinal fluid
for analysis. Because each ADDL protein alters several
hundred strands of DNA, its signature is vastly amplified,
enough to be detected by standard DNA barcode-reading
techniques.
HYPER
SENSITIVE
The researchers, who announced their findings February
4 in the Proceedings of the National Academy of Sciences,
describe the test as a million times more sensitive
than any other diagnostic test.
"This study is a major step forward
in identifying a routine diagnostic tool for Alzheimer's
disease, and it validates our hypothesis that there
are many biomarkers for disease that go under the radar
of conventional diagnostic tools," said senior author
Dr Chad Mirkin of Northwestern University. "The extraordinary
sensitivity of the barcode assay has a chance to change
the way the medical community thinks about molecular
diagnostics and the markers they consider for many types
of diseases."
"It's a good bet that the very
earliest stage of AD memory loss begins when ADDLs attack
key synapses in the brain," said study co-author Dr
William Klein, PhD, also of Northwestern University.
"Thanks to the extraordinary sensitivity of the BCA
it's been possible to validate the prediction, and maybe
even set the stage for creating the first clinical lab
test for Alzheimer's disease."
As this is the first test for pre-symptomatic
Alzheimer's patients, there's little evidence on what
earlier intervention might achieve. For the moment,
we may only have a new test for an incurable disease.
PNAS published online Feb
4, 2005
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