|
 The report in Nature Medicine describes a woman from a Colombian
family whose members carry a gene called presenilin-1 that
predisposes them to develop early-onset Alzheimer's, typically in
their 40s, said study coauthor Dr. Eric Reiman, executive director
of the Banner Alzheimer's Institute in Phoenix, Arizona.
"In this case, the person didn't develop cognitive impairment for
nearly 30 years after that," Reiman said.
The difference, scientists believe, is that the woman also carried
two copies of a rare mutation in the APOE3 gene called APOE3
Christchurch. Scientists believe these mutations helped delay signs
of cognitive decline until the woman was in her 70s.
It's well known that abnormal versions of two proteins, amyloid and
tau, are involved in Alzheimer's disease. Amyloid forms plaques
outside of brain cells, while tau forms tangles within the cells.
Many drugs being studied to prevent dementia focus on removing
amyloid, but this woman's case suggests tau might be the real
culprit.
Presenilin-1 increases accumulation of amyloid, which was present in
abundance in the brain of the woman in the study. "This is a person
who has been overproducing amyloid since birth," Reiman said. But
she had little tau clogging her neurons and she has remained
cognitively intact far longer than other members of her family.
The two copies of APOE3 Christchurch apparently protected her mental
abilities despite all the amyloid plaques, the researchers say.
The data suggest that APOE3 Christchurch blocks a crucial step
that's thought to trigger tau accumulation and other toxic events
leading to neurodegeneration and cognitive impairment, said coauthor
Yakeel Quiroz, director of the familial dementia neuroimaging lab at
Massachusetts General Hospital and Harvard Medical School in Boston,
in an email.
[to top of second column] |
The findings turn some of the Alzheimer's dogma on its head, said
Dr. Samuel Gandy, associate director of the Alzheimer's Disease
Research Center at the Icahn School of Medicine at Mount Sinai in
New York City.
Those dogmas are: amyloid is the protein harming the brain and the
importance of the APOE gene is in the APOE4 variation, which seems
to speed the disease, Gandy said.
"This paper will cause an earthquake among those of us spending our
lives trying to match up clinical manifestations with genetic
mistakes," Gandy said in an email. "It's back to the drawing board
for us."
Earlier studies had suggested tau protein might be the primary
perpetrator in dementia, said Tamar Devora Gefen, a
neuropsychologist and associate director of the clinical core of the
Northwestern Alzheimer's Disease Center in Chicago.
Most trials so far "focused on the obliteration of amyloid," Gefen
said in an email. "This study, like many others, shifted its focus
onto tau, which is a necessary step towards intervention discovery."
The study "is yet another example of the power of 'one' — a single
case study that has the potential to impact many," Gefen said.
SOURCE: https://go.nature.com/2C7QDrF and https://go.nature.com/2Nj51DT
Nature Medicine, online November 4, 2019.
[© 2019 Thomson Reuters. All rights
reserved.] Copyright 2019 Reuters. All rights reserved. This material may not be published,
broadcast, rewritten or redistributed.
Thompson Reuters is solely responsible for this content. |
