Summary: A new study reports on the role the protein TDP-43 plays in the development of Alzheimer’s disease.
Source: Rush University Medical Center.
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“This finding could help researchers to understand the cause of
memory loss and lead to new ways to approach studying Alzheimer’s disease,”
said Bryan James, PhD, study author and epidemiologist with the Rush
Alzheimer’s Disease Center. “Our study found that when the main characteristic
pathologies of Alzheimer’s disease, plaques and tangles, were mixed with a
pathologic protein called TDP-43 in the brain, the combination was more likely
to result in diagnosed Alzheimer’s dementia than plaques and tangles alone.”
The abnormal protein, TDP-43 (short for ‘hyperphosphorylated
transactive response DNA-binding protein 43’), previously has been associated
with frontal temporal dementia and amyotrophic lateral sclerosis (ALS,
sometimes called Lou Gehrig’s disease). In recent years, TDP-43 also has been
found in the brains of persons with other diseases, but most recently in
Alzheimer’s disease.
Mixed pathologies increase Alzheimer’s risk
The hallmark pathologies of Alzheimer’s disease are the
accumulation of the protein beta-amyloid (called plaques) and an abnormal form
of the protein tau (called tangles). However, research from the Rush
Alzheimer’s Disease Center and other groups has shown that the majority of
persons with clinical Alzheimer’s dementia also develop other disease
pathologies in their brains as well, such as small strokes or protein deposits
called Lewy bodies.
This combination, called ‘mixed pathologies,’ increases the risk
for developing diagnosed Alzheimer’s dementia above and beyond just having
plaques and tangles in the brain.
“The clinical disease that we call ‘Alzheimer’s disease’ is
looking more and more like the result of the accumulation of a number of
disease processes in the brain of older persons,” James said. The majority of
persons with diagnosed Alzheimer’s dementia actually have mixed pathologies in
their brains — not just the plaques and tangles that are the known hallmarks of
Alzheimer’s disease.
“In particular, mixed Alzheimer’s and TDP-43 pathologies appear
to be an under-recognized yet common form of mixed pathologies that contributes
to the development of clinical Alzheimer’s dementia,” James said. “This is one
of the first studies to examine TDP-43 and Alzheimer’s disease in the context
of mixed pathologies.”
TDP-43 found in two-thirds of those with Alzheimer’s dementia
The Brain paper built on previous research by examining whether TDP-43
was associated with an increased likelihood of a diagnosis of Alzheimer’s
dementia in persons both with and without pathologic Alzheimer’s disease. The
new study examined brain pathology, drawing on tissue samples from 946 deceased
older men and women who had been enrolled in one of two cohort studies by the
Rush Alzheimer’s
Disease Center, the Rush Memory and Aging Project or the Religious
Orders Study. Participants in both studies agree to donate their brains to
research after their death.
TDP-43 was present in the brains of about half of the
participants and in two-thirds of the brains of persons who had been diagnosed
with Alzheimer’s dementia while alive. More than a third of the participants
had mixed Alzheimer’s (plaques and tangles) and TDP-43 pathologies in their
brain. Mixed Alzheimer’s and TDP-43 pathologies were associated with a higher
likelihood of diagnosed Alzheimer’s dementia at death than plaques and tangles
alone.
“These data are exciting, because an improved understanding of
the TDP-43 protein has potential to guide alternative treatment strategies for
Alzheimer’s disease,” James said.
ABOUT THIS ALZHEIMER’S DISEASE RESEARCH ARTICLE
Source: Nancy Difiore – Rush University Medical Center
Image Source:
NeuroscienceNews.com image is in the public domain.
Original Research: The study
will appear in Brain.
