JANUARY/FEBRUARY 2020. DISCOVER 55New Form of
Dementia Strikes
the ‘Oldest Old’
BY LINDA MARSA
i
So many older people experience the telltale
symptoms of Alzheimer’s disease, like forgetful-
ness and muddled thinking. Yet postmortem
autopsies often find none of the amyloid plaques or
tau tangles that are hallmarks of the mind-robbing
illness. Now, scientists may have solved this perplex-
ing mystery: These patients are probably affected by
a newly identified degenerative disorder that mim-
ics Alzheimer’s and may be just as prevalent among
older adults.
Called LATE (limbic-predominant age-related
TDP-43 encephalopathy), it mainly affects the “oldest
old” — generally people older than 85. It also seems
to be associated with deposits of an errant version of a
protein called TDP-43, which collect in brain regions
governing memory, like the hippocampus and middle
frontal gyrus, as well as areas that regulate emotions
and survival instincts, like the amygdala. Roughly
1 in 4 people older than 85 have a buildup of this
protein in these sections of the brain, suggesting the
disorder may be as much of a public health threat in
this age group as is Alzheimer’s.
Over the past decade, scientists noticed about a
third of neuroimaging scans and cerebrospinal fluid
analyses on living patients with memory problems
came back negative for Alzheimer’s. Instead of the
expected tau or amyloid deposits, “we’d look under
the microscope and there was some other protein
that was accumulating,” says Julie Schneider, asso-
ciate director of Rush University Medical Center’s
Alzheimer’s Disease Center in Chicago.
Slowly, the puzzle pieces started falling into place.
This appeared to be a different illness. “We all had
clues and noticed different bits and pieces, but no one
had a complete picture,” says Peter Nelson, a neuro-
pathologist specializing in dementia-related research,
including Alzheimer’s, at the University of Kentucky.
Finally, in a paper published in the journal Brain in
April, scientists from numerous disciplines gathered
everything they knew about this disorder to create
a resource that could be used as a foundation for
further research. They agreed upon the name LATE,
and described its symptoms and the affected brain
regions. They also identified the probable culprit
— the errant TDP-43. In addition, they suggested
diagnostic tools and strategies for targeted therapies
that could thwart the abnormal protein.
“The more we understand,” says Nina Silverberg,
director of the Alzheimer’s Disease Research Centers
Program at the National Institute on Aging, “the
better hope we have of finding a treatment.”Neuropathologist Peter Nelson (above) analyzed
dementia patients’ brains postmortem (below).