An account of Alzheimer's using motor car metaphors
- From: Lance <LanceGary@xxxxxxxxx>
- Date: Tue, 18 Mar 2008 06:42:39 -0700 (PDT)
Paradoxical Alzheimer's Finding May Shed New Light On Memory Loss
ScienceDaily (Mar. 16, 2008) — Do you remember the seventh song that
played on your radio on the way to work yesterday? Most of us don't,
thanks to a normal forgetting process that is constantly "cleaning
house" -- culling inconsequential information from our brains.
Researchers at the Buck Institute now believe that this normal memory
loss is hyper-activated in Alzheimer's disease (AD) and that this
effect is key to the profound memory loss associated with the
incurable neurodegenerative disorder.
Last year, this same group of researchers found that they could
completely prevent Alzheimer's disease in mice genetically engineered
with a human Alzheimer's gene--"Mouzheimer's"--by blocking a single
site of cleavage of one molecule, called APP for amyloid precursor
protein. Normally, this site on APP is attacked by molecular scissors
called caspases, but blocking that process prevented the disease.
Now they have studied human brain tissue and found that, just as
expected, patients suffering from AD clearly show more of this
cleavage process than people of the same age who do not have the
disease. However, when they extended their studies to much younger
people without Alzheimer's disease, they were astonished to find an
apparent paradox: these younger people displayed as much as ten times
the amount of the same cleavage event as the AD patients. The
researchers now believe they know why.
The Buck Institute study implicates a biochemical "switch" associated
with that cleavage of APP, causing AD brains to become stuck in the
process of breaking memories, and points to AD as a syndrome affecting
the plasticity or malleability of the brain. The study, due to be
published in the March 7 issue of the Journal of Alzheimer's Disease,
provides new insight into a molecular event resulting in decreased
brain plasticity, a central feature of AD.
"Young brains operate like Ferraris -- shifting between forward and
reverse, making and breaking memories with a facility that surpasses
that of older brains, which are less plastic," said Dale Bredesen, MD,
Buck Institute faculty member and leader of the research group. "We
believe that in aging brains, AD occurs when the 'molecular shifting
switch' gets stuck in the reverse position, throwing the balance of
making and breaking memories seriously off kilter."
In previous research, lead author Veronica Galvan, PhD, prevented this
cleavage in mice genetically engineered to develop the amyloid plaques
and deposits associated with AD. These surprising mice had normal
memories and showed no signs of brain shrinkage or nerve cell damage,
despite the fact that their brains were loaded with the sticky A-beta
plaques that are otherwise associated with Alzheimer's disease.
"A-beta is produced throughout the brain throughout life; we believe
that it is a normal regulator of the synapses, the connections between
neurons," said Galvan, who added that AD, like cancer, is a disease in
which imbalanced cell signaling plays an important role.
"The fact that many people develop A-beta plaques yet show no symptoms
of AD tells us that the downstream signaling of A-beta--not just A-
beta itself--is critical," said Bredesen, "and these pathways can be
targeted therapeutically. Simply put, we can restore the balance."
Continuing research at the Buck Institute focuses on nerve signaling
and efforts to "disconnect" the molecular mechanism that throws memory-
making in the reverse direction, as well as understanding mechanisms
that support brain cell connections that are crucial to the process of
memory making.
AD is an incurable neurodegenerative disease currently affecting 5.1
million Americans. AD results in dementia and memory loss, seriously
affecting a person's ability to carry out activities of daily living.
AD costs the U.S. $148 billion annually, in addition to untold family
suffering.
Joining Bredesen and Galvan as co-authors of the paper, "C-terminal
cleavage of the amyloid precursor protein at Asp664: a switch
associated with Alzheimer's disease" are Surita Banwait, BA; Junli
Zhang, MD; Olivia F. Gorostiza, Marina Ataie, BS; Wei Huang, BS; and
Danielle Crippen, BA of the Buck Institute, as well as Edward H. Koo,
MD, of the University of California, San Diego, Department of
Neuroscience. The work was supported by the Joseph Drown Foundation,
The National Institute on Aging, the Bechtel Foundation, and the
Alzheimer's Association.
Adapted from materials provided by IOS Press, via EurekAlert!, a
service of AAAS.
IOS Press (2008, March 16). Paradoxical Alzheimer's Finding May Shed
New Light On Memory Loss. ScienceDaily. Retrieved March 18, 2008, from
http://www.sciencedaily.com/releases/2008/03/080312164838.htm
.
- Prev by Date: White matter withering = woeful walking
- Next by Date: Re: The atheist delusion
- Previous by thread: White matter withering = woeful walking
- Next by thread: Re: Terrible threat to science - a Grim warning
- Index(es):
Relevant Pages
|
