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Clues behind defying the fate of
predetermined Alzheimer’s genetics
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While seeking the secrets behind unlocking Alzheimer’s disease, a major
clue may have been uncovered through careful genetic analysis. A man
genetically fated to suffer memory loss in his 40s or 50s, based on family
history and inherited genes, maintained normal cognitive function far
longer than expected. He is believed to have been provided protection by
a rare gene that provided downstream cellular function towards nerve cell
communication.
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The man and members of his family inherited a mutated gene
called presenilin-1, or PSEN1. Carriers of this gene are almost certain
to develop early-stage Alzheimer’s disease. Following his death
and medical examination, his brain was loaded with beta amyloid
and tau, two proteins that accumulate in the brains of Alzheimer’s
disease patients. However, he did not develop mild dementia until
age 72, before passing away from pneumonia at 74, exceeding his
cognitive decline expectations and staving off Alzheimer’s.
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Upon further genetic analysis, it was revealed that this man had a
rare change in a gene that codes for a protein called reelin, which
helps nerve cells communicate. The enhanced reelin protein
seemed to be protecting a very specific part of the man’s brain, an
area that sits behind the nose at the base of the brain called the
entorhinal cortex. It’s an area of the brain that also sends and
receives signals related to the sense of smell. Loss of smell is often a
harbinger of brain changes that lead to memory and thinking
difficulties.
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Dr. Joseph Arboleda-Velasquez, an associate professor of
ophthalmology at Harvard University and lead author of a new study on
the man, states: “In this case, it was very clear that this reelin variant
makes reelin work better. That gives us a huge insight. It makes it very
obvious that just putting more reelin in the brain may actually help
patients. Another big insight from this case is, it seems like maybe you
don’t need this everywhere in the brain. When people have Alzheimer’s, it
starts in the entorhinal cortex, and then it spreads.”
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