The Yin and Yang of Alzhiemer’s Disease
Researchers believe an imbalance of
peptides leads to Alzhiemer’s progression.
Photo Credit: Rensselaer Polytechnic Institute/Caitlin
Chunyu Wang, assistant professor of biology, is challenging
current thinking on the causes and prevention of Alzheimer’s
disease, offering a new hypothesis that could be the key to
preventing this form of dementia. He has found that a specific
imbalance between two peptides may be the cause of the fatal
neurological disease that affects more than five million people
in the United States.
“We have found that two peptides, Aβ42 and Aβ40, must be in
balance for normal function,” said Wang. “They are like the Yin
and Yang in Taiji, an ancient Chinese philosophy. When the
peptides are produced in the correct proportions, the brain is
healthy; but when that delicate balance is changed,
pathological changes will occur in the brain and the person’s
memories become hazy, leading to eventual dementia.”
Wang expects that this imbalance could be the main factor in
the progression of Alzheimer’s disease. If correct, the
addition of Aβ40 may stop the disease’s development. Wang notes
that further research is needed, but his preliminary results
challenge the current mode of thinking about how these peptides
contribute to the progression of the disease.
The research will be published in the June edition of the
Journal of Molecular Biology.
Peptides are formed by the linking of different amino acids.
The two peptides that Wang investigated were both Amyloid
β-peptides (Aβ) — specifically those composed of 40 and 42
amino acids, called Aβ40 and Aβ42. These two peptides have been
previously found in deposits, called senile plaques or amyloid
plaques, in brains afflicted with Alzheimer’s disease. These
plaques, mainly composed of Aβ42 fibrils, are a hallmark of
Prior research has uncovered that increased levels of Aβ42
become toxic to brain cells when individual molecules of Aβ42,
or monomers, combine to form oligomer or fibril chains. This
process is called aggregation. But the role of Aβ40, which is
also found in senile plaques and generated from the same
protein as Aβ42, has not been clearly established. Wang set out
to determine what role this peptide played in the generation of
Wang used the advanced Nuclear Magnetic Resonance (NMR)
machines within the Center for Biotechnology and
Interdisciplinary Studies to monitor the formation of harmful
Aβ42 fibrils in the presence of different levels of
As levels of Aβ40 decrease, levels of
harmless Aβ42 monomers also decrease as the monomers form
Photo Credit: Rensselaer Polytechnic Institute/Yilin
Using NMR data, Wang found that as Aβ40 levels increased,
the aggregation of Aβ42 fibrils sharply decreased, protecting
benign Aβ42 monomers.
Wang’s experiments show that when there is 15 times more
Aβ40 than Aβ42, the formation of Aβ42 fibrils is almost
completely stopped. “This means that the introduction of Aβ40
to tip the peptide balance toward Aβ40 could potentially halt
or slow down the progression of the Alzheimer’s in the human
brain,” Wang said.
Wang plans to continue investigating how Aβ40 halts the
formation of Aβ42 fibrils, and he already sees vast
implications for this change in thinking about the progression
of the disease.
“This has the potential to become a simple therapy to
prevent the formation of toxic Aβ42 species,” he said. “I plan
to continue my research on the role of Aβ40 and hope that we
can test this theory on human neurons, animal models, and
someday in clinical trials.”
The research was funded by the Alzheimer’s Association and a
New York State Office of Science, Technology, and Academic
Research (NYSTAR) James D. Watson Investigator Program
Rensselaer graduate student Yilin Yan worked with Wang on
the research project.