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Plasma protein appears to be associated with
development and severity of Alzheimer's
disease
July 2010--Higher concentrations of clusterin, a protein in
the blood plasma, appears to be associated
with the development, severity and
progression of Alzheimer's disease,
according to a report in the June issue of
Archives of General Psychiatry, one
of the JAMA/Archives journals.
Individuals with Alzheimer's disease display several
findings in their blood and cerebrospinal
fluid that may reflect neuropathological
changes, according to background information
in the article.
For instance, in cerebrospinal fluid, individuals with
Alzheimer's disease have lower levels of
amyloid-beta peptides and higher levels of
total and phosphorylated tau concentration,
which reflect the formation of hallmark
plaques and tangles in the brain.
Similarly, numerous articles have suggested that levels of
certain metabolites and proteins in the
plasma might represent responses to brain
changes in Alzheimer's disease, but none
have been replicated.
Madhav Thambisetty, M.D., Ph.D., of Institute of
Psychiatry, King's College London, and
colleagues used a combined proteomic and
neuro-imaging approach to identify plasma
proteins associated with Alzheimer's disease
pathology.
Participants in two studies—some with Alzheimer's
disease, some with its precursor mild
cognitive impairment and some with no
dementia—underwent standardized clinical
assessments and brain imaging scans.
Their blood plasma was then assessed for proteins that may
be associated with Alzheimer's disease.
Based on findings of two "discovery phase" studies in 95
patients, one protein, clusterin, appeared
to be associated with atrophy of the
hippocampal region of the brain and with
rapid progression of cognitive decline.
The researchers then studied clusterin levels in all 689
participants (including 464 with Alzheimer's
disease) and found an association between
higher plasma levels of the protein and
severity of disease, rapid clinical
progression and atrophy in the brain area
known as the entorhinal cortex, which plays
a role in memory.
In addition, increased clusterin levels in the plasma were
associated with having more amyloid-beta—which
forms the brain plaques associated with
Alzheimer's disease—in the brain's medial
temporal lobe.
According to the authors, "previous studies suggest that
clusterin belongs to a family of
extracellular chaperones," proteins that
regulate the formation and removal of
amyloid.
"Although these findings do not support the clinical
utility of plasma clusterin concentration as
a stand-alone biomarker for Alzheimer's
disease, they reveal a robust peripheral
signature of this amyloid chaperone protein
that is responsive to key features of
disease pathology."
"Our findings clearly implicate clusterin, but there may
well be other proteins in plasma related to
the disease process, and indeed our previous
studies and those of others suggest this is
the case," they conclude.
"These results may have wider implications for the
identification of other amyloid chaperone
proteins in plasma, both as putative
Alzheimer's disease biomarkers as well as
drug targets of disease-modifying
treatments."
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