Study reveals new link between Alzheimer's
disease and healthy aging
August 16, 2011 – Alzheimer's disease and
frontotemporal lobar degeneration (FTLD) are
two of the most prevalent forms of
neurodegenerative disorders. In a study
published online today in Genome Research (www.genome.org),
researchers have analyzed changes in gene
expression in the aging and diseased brain,
finding new clues to the biology of normal
aging and neurodegenerative diseases.
Recent studies have identified changes in
how genes are read, or expressed, in the
brain either during aging or with
neurodegenerative disease. However, no
previous study had directly compared gene
expression changes in healthy aging with
those in diseased individuals.
In this report, an international team of
researchers analyzed and compared changes in
gene expression associated with aging and
disease in a region of the brain known to be
affected in both Alzheimer's and FTLD.
Comparing samples from healthy individuals
ranging from 16 to 102 years old with
samples from diseased individuals, the
investigation uncovered striking similarity
in the changes in gene expression patterns
associated with aging and the
neurodegenerative diseases.
"Surprisingly, these [diseased] samples
contained the same aging-related changes as
healthy individuals over the age of 80,"
said Dr. Jernej Ule of the MRC Laboratory of
Molecular Biology, senior author of the
study.
"Aging-related changes were apparent in the
diseased individuals as young as 50 years,"
noted Dr. James Tollervey of the MRC
Laboratory of Molecular Biology, the first
author of the study, "roughly 25 years
before we would expect to see similar
changes in healthy individuals."
While the similarities were striking, the
group also observed notable differences
between gene expression in the normal aging
brain and expression in Alzheimer's and FTLD,
particularly in the patterns of alternative
splicing, a process by which parts of a RNA
molecule are arranged differently to change
the message, which can be potentially
harmful if misregulated.
In normal aging, changes in alternative
splicing largely affected genes associated
with cellular metabolism, while
disease-specific changes were associated
with genes involved in neuron-specific
function.
The group found that there were changes in
the expression of several genes coding for
RNA binding proteins, which is likely
responsible for at least part of the
observed alterations in splicing.
The authors expect that this work will have
broad impact for further insight into both
normal aging and neurodegenerative disease.
"These findings indicate that studies of
healthy aging could help unravel the
processes that lead to neurodegeneration,"
said Ule.
"Conversely, our findings also indicate that
studies of neurodegenerative diseases might
help us understand how to delay the changes
that take place in healthy individuals at an
advanced age," added Dr. Boris Rogelj of the
MRC Centre for Neurodegeneration Research at
King's College London, a co-author of the
study.
