July 17, 2011
Two Studies Advance Global Standardization of Biomarkers for Alzheimer’s Disease
moves closer to new and earlier tests for the disease, innovative global
research initiatives are taking the first important steps to standardize
Alzheimer's biomarkers, as evidenced by two presentations made today at the
Alzheimer's Association(R) International Conference 2011 (AAIC 2011) in
One study compared, for the first time, results of brain amyloid imaging
and the impact of genetics and ethnicity on those results across countries on
three different continents as part of a worldwide Alzheimer's disease imaging
study. The other takes a significant step forward in creating a standard
international method for measuring the size of a key memory center in the
brain (the hippocampus) - which often is one of the first brain areas affected
"We need to identify people in the earliest stages of Alzheimer's, even
those without outward evidence of memory and thinking symptoms, for treatment
and prevention trials," said
and Scientific Relations at the Alzheimer's Association. "It is very important
that the tests are accurate and effective, and that they are delivered and
measured in the same way across the world so that measures are comparable."
"For example, if you get your blood tested for cholesterol levels in
comparable. That is not yet the case for Alzheimer's disease, especially for
assays that detect Alzheimer's proteins in blood or cerebrospinal fluid,"
Carrillo said. "To ensure comparable results, the methods used for gathering
and evaluating samples must be consistent. As an illustration, spinal fluid
gathered or stored in a plastic container may give different results than a
sample gathered or stored in a glass container."
The Alzheimer's Association is taking the lead in a number of global
efforts to standardize Alzheimer's biomarkers, in particular with the creation
and management of the World Wide Alzheimer's Disease Neuroimaging Initiative
(WW-ADNI) and the Alzheimer's Association Cerebrospinal Fluid (CSF) Quality
WW-ADNI is the umbrella organization for neuroimaging initiatives being
carried out through the North American ADNI, European ADNI (E-ADNI), Japanese
ADNI, Australian ADNI (AIBL), and Taiwan ADNI. The overall goals of WW-ADNI
are to better understand the physical changes that occur in healthy
individuals compared with individuals with mild cognitive impairment (MCI) and
Alzheimer's, and to develop improved methods for identifying the appropriate
patient populations for clinical trials. WW-ADNI also aims to standardize the
methods used for conducting imaging scans and gathering and testing fluid
samples so that data from all sites can be readily combined and easily
understood by researchers. Data from WW-ADNI are expected to play a key role
in identifying effective treatments for Alzheimer's, as well as methods that
may prevent or slow the progression of the disease.
Launched in fall 2009, the Alzheimer's Association Cerebrospinal Fluid
(CSF) Quality Control Program brings together laboratories across the globe
with the aim of standardizing the measurement of potential Alzheimer
biomarkers. More than 60 labs in North and
in aiding early detection of Alzheimer's and improving diagnostic accuracy,
but also in identifying and monitoring the effects of drugs in clinical
trials, understanding the molecular changes that lead to Alzheimer's, and
helping to ensure that individuals recruited into Alzheimer clinical trials
are on a path toward developing the disease. The program is fully supported by
a gift from the
"To enable people to live their lives without the dementia caused by
Alzheimer's, early detection of the disease and effective treatment are
essential," Carrillo said. "These two research efforts, and others like them,
will be instrumental in getting us there."
Alzheimer's Disease Neuroimaging Data from Three Countries
It has not been established whether the association between a well-
established Alzheimer's risk gene - apolipoprotein E (APOE) e4 - age, and
amyloid deposition is consistent among ethnic groups.
colleagues, used data from three multi-center studies of Alzheimer's that are
using a harmonized protocol - the Alzheimer's Disease Neuroimaging Initiative
(US-ADNI), Australian Imaging Biomarker and Lifestyle Flagship Study of Aging
(AIBL), and Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) - to
evaluate the influence of APOE e4 and age on the accumulation of amyloid in
the brain as measured by PET scan with 11C-
is the first report of an international ADNI data analysis including these
three different national populations, all three of which include people with
Alzheimer's, MCI, and cognitively normal individuals.
The researchers found that:
The effect of age and APOE-e4 on amyloid deposition in the Japanese
population is similar to Caucasians, despite a lower e4 allele frequency in
the Japanese population.
In the cognitively normal people in the study, having a single copy of the
APOE-e4 gene is roughly equivalent to 12 additional years of age for PiB
Perhaps most importantly, for the Alzheimer's research field, the results
suggest that the three multi-national ADNI data sets are feasible for combined
"This is one of the first demonstrations of the great value of open data
sharing in the worldwide ADNI initiative," Ishii said. "Combined analysis
enlarges and diversifies the study population and the data set. It increases
the power of the results, decreases ethnicity effects and makes the findings
more broadly applicable. This is very important as we identify and verify
biomarker tests for Alzheimer's disease."
Towards a Harmonized Protocol for Measuring the Hippocampus
The earliest Alzheimer's related brain changes are usually seen in the
hippocampus, the "control center" of memory-related activity in the brain. In
previous studies, MRI measurement of shrinkage of the hippocampus over time
has shown value for diagnosis of Alzheimer's and tracking the progression of
the disease. But harmonization (greater standardization) in assessing volume
change is needed as researchers work to move hippocampal measurement from
research centers into wider clinical use.
A variety of published protocols now exist for assessing hippocampal
volume. These protocols differ because they rely on various techniques of
"segmentation" - that is, assigning the electronic image voxels (volumetric
pixels) to specific structures, such as the hippocampus, within the brain.
As a first phase of the standardization process,
of San Giovanni di Dio Fatebenefratelli, Brescia,
surveyed the various available segmentation protocols to identify underlying
reasons why they result in different volume estimates. This work was funded by
the Alzheimer's Association.
"The next step will be to create, test and verify a single protocol for
MRI-based evaluation of Alzheimer's disease-related hippocampal shrinkage,"
Frisoni said. "This initial quantification will help our international panel
of experts define which key components should be included in an international
The Alzheimer's Association International Conference (AAIC) is the world's
largest conference of its kind, bringing together researchers from around the
world to report and discuss groundbreaking research and information on the
cause, diagnosis, treatment and prevention of Alzheimer's disease and related
disorders. As a part of the Alzheimer's Association's research program, AAIC
serves as a catalyst for generating new knowledge about dementia and fostering
a vital, collegial research community.
About the Alzheimer's Association
The Alzheimer's Association is the world's leading voluntary health
organization in Alzheimer's care, support and research. Our mission is to
eliminate Alzheimer's through the advancement of research, to provide and
enhance care and support for all affected, and to reduce the risk of dementia
through the promotion of brain health. Our vision is a world without
Alzheimer's. Visit www.alz.org or call 800-272-3900.
SOURCE Alzheimer's Association