Alzhiemers
AlzhiemersBrain cell research offers hope for
Alzheimer's
NEW YORK, Feb 28 (Reuters Health) -- Taking cells from a
region of the brain known as the hippocampus, an international
team of researchers have grown functional brain cells in lab
cultures. The findings may have profound implications for
restoring damaged or degenerative brain cells, which occurs in
diseases such as Alzheimer's and Parkinson's.
The brain has recently been shown to regenerate some of its cells,
but scientists were unable to identify the cells, known as stem
cells, that gave rise to the new brain neurons. The technique used
in this study now gives scientists the ability to identify those stem
cells in the brains of living patients, and shows that these cells can
be stimulated to turn into new neurons, principal author Dr.
Steven A. Goldman told Reuters Health.
In addition, it may lead to the development of drugs that would
stimulate the formation of new brain cells in people with
Alzheimer's or other diseases where brain cells degenerate, he
commented.
Goldman noted that the use of drugs to stimulate proliferation of
new brain cells will probably result in a more successful strategy
than attempting to grow the cells outside the body and then
placing them back into the brains of patients, as some scientists
have suggested.
Goldman, of Cornell University Medical College in New York,
and colleagues surgically extracted brain cells from the
hippocampus of eight living male patients, ranging in age from 5 to
63 years, while they underwent surgery for another reason. The
investigators isolated stem cells from the brain tissue. The stem
cells were then grown in culture along with certain factors known
to control the development of neurons.
The cells gave rise to functional neurons, Goldman's team reports.
``The adult human hippocampus contains... progenitor cells that
can give rise to new neurons,'' the authors write in the March
issue of Nature Medicine. They add that ``the isolation of these
cells may provide a... substrate for re-populating the damaged or
degenerated adult hippocampus.''
In an accompanying commentary, Dr. Jack P. Antel and
colleagues of the McGill University in Montreal, Canada, say that
the study ``opens up the possibility'' of transplanting lab-grown
brain cells into patients.
However, in response, Goldman said, ``I think I would add a
word of caution in terms of the transplantation emphasis,'' adding
that the practical limitations ``may be daunting.'' Goldman added
that transplantation ``may be feasible on an experimental basis in
just a few years, but I don't think it will become a widespread
therapeutic technique.'' SOURCE: Nature Medicine
2000;6:249-250, 271-277.
Alzheimer's risk factor explained
By Penny Stern, MD
NEW YORK, Mar 02 (Reuters Health) -- Alzheimer's disease
has been the focus of intense research for decades. A new study
published in the Proceedings of the National Academy of
Sciences may help unravel the mystery of why the presence of a
particular protein in the brain leads to the dementia and
degeneration associated with this dreaded disease.
Dr. David M. Holtzman of the Washington University School of
Medicine in St. Louis, Missouri, together with colleagues there
and at the Lilly Research Laboratories in Indianapolis, Indiana,
studied mice to explore how apolipoprotein E (apoE) influences
amyloid-beta plaque-forming deposits in the brain.
The accumulation of this amyloid protein in the brains of
Alzheimer's patients is believed responsible for the damage done
to brain nerve cells, Holtzman told Reuters Health.
``In this study, we show that an interaction between apoE and
amyloid-beta is critical not only for the buildup of amyloid-beta,
but also for an important part of its toxicity in the brains of living
animals,'' he said.
There are several variants of apoE and earlier work seemed to
indicate a greater risk for Alzheimer's disease attached to the
presence of the apoE4 form of the protein, although the specific
mechanism was unclear.
Study co-author, Dr. Steven M. Paul of Lilly Research
Laboratories, explained to Reuters Health that the apoE gene is
actually ``a risk factor gene. If you have two copies of the
E4-variant, you have about a 10-fold greater risk of getting
Alzheimer's disease.'' He added that ``about half the people with
two copies will get the disease by age 65 and about 80% will get
it by age 85.'' In contrast, the presence of the apoE2 variant is
protective and reduces the risk of Alzheimer's.
Interestingly, about 10% of people with two copies of the apoE4
gene will never get the disease and Paul speculates that another
factor may need to be superimposed on this genetic background
to allow the disease to occur.
According to Holtzman, ``the apoE4 variant is much worse (than
other human variants) in causing the toxicity'' because it seems to
encourage more amyloid deposition and the formation of nerve
tangles and plaques in areas of the brain that function in learning
and memory.
Thus, Holtzman said, ``apoE4 appears to be a critical element'' in
producing the kinds of tissue changes that ultimately contribute to
the impairments characteristic of Alzheimer's.
Studies such as these ``indicate that modification of human apoE
levels or interactions with amyloid-beta, will modify Alzheimer's
disease,'' he said, which may open the way for innovative
strategies to treat or perhaps prevent the disease.
Paul concurs. ``If we could find a way to reduce apoE
expression, since we know what cells make it in the brain, we
think we could come up with a drug that might prevent plaque
deposition,'' he said.
Holtzman and Paul both subscribe to the prevailing amyloid
deposition cascade theory of Alzheimer's disease development
and believe that drugs could conceivably ``prevent and certainly
reverse Alzheimer's disease,'' Paul added.
He cautions, however, that such a medication is likely some years
away from the market but that the current study is an important
step ``in solving the genetic riddle'' of Alzheimer's. SOURCE:
Proceedings of the National Academy of Sciences Early Edition
March 14, 2000.