A protein linked to higher risk of Alzheimer’s can be removed from
the brains of mice without hindering memory and learning, according to a
study that addresses whether potential therapeutics targeting this
protein would have detrimental side effects.
The study from the Peter O’Donnell Jr. Brain Institute
also showed, however, that the protein’s absence in other parts of the
body hinders brain function as blood cholesterol levels rise. This
result substantiates previous research that indicated cardiovascular
health affects the brain.
Researchers focused on the removal of apolipoprotein E (ApoE), which
in a certain form can support the buildup of toxic plaques in the brains
of Alzheimer’s patients. Studies elsewhere have sought to determine
whether reducing ApoE could be an effective treatment in preventing the
disease, but a lingering question has been whether the protein is
necessary for healthy brain function.
The study found that mice can maintain their learning and memory when
virtually all ApoE is removed from the brain but kept present in the
liver to filter cholesterol. Mice that lacked ApoE in both the brain and
liver experienced unhealthy cholesterol levels and lost cognitive
More research is needed to determine what causes the cardiovascular issues to affect the brain, said Dr. Joachim Herz,
the study’s Principal Investigator and Professor of Molecular Genetics,
Neuroscience, Neurology and Neurotherapeutics at the O’Donnell Brain
Institute at UT Southwestern Medical Center.
But the findings, published in The Journal of Neuroscience,
add support to the belief that reducing ApoE in the brain could
eventually be a viable therapeutic option for treating Alzheimer’s.
“This approach still holds potential,” said Dr. Herz, holder of the
Thomas O. and Cinda Hicks Family Distinguished Chair in Alzheimer’s
Disease Research and Director of the Center for Translational Neurodegeneration Research.
ApoE has several roles in the body, including transporting
cholesterol and related molecules such as b-amyloid that form plaques in
the brains of Alzheimer’s patients if not properly filtered or removed.
The type of ApoE produced by the ApoE gene determines how effectively
the amyloid is removed from the brain. ApoE2 is the most effective,
ApoE3 is in the middle and ApoE4 is the most likely to allow for the
buildup of amyloid plaques. People whose genes produce ApoE4 are at high
risk of developing Alzheimer’s.
Studies are ongoing at UT Southwestern and elsewhere to further
understand the various effects that ApoE4 removal has on brain and body