Chronic inflammation in the brain is precursor to Alzheimer's
11 July 2012
Chronic inflammation from infection can predispose the brain
to develop Alzheimer’s disease later in life, according to Swiss
Researchers from the University of Zurich, in collaboration with
colleagues from the ETH Zurich and University of Bern investigated
what impact immune system challenges (similar to having a severe
viral infection) would have on the development of AD in mice.
Results showed that a single infection before birth (during late
gestation) was enough to induce long-term neurological changes and
significant memory problems at old age.
These mice had a persistent increase in inflammatory cytokines,
increased levels of amyloid precursor protein (APP), and altered
cellular localization of Tau. If this immune system challenge was
repeated during adulthood the effect was strongly exacerbated,
resulting in changes similar to those seen for pathological aging.
To date it has been difficult to pin down the role of
inflammation in Alzheimer’s disease (AD), especially because trials
of NSAIDs appeared to have conflicting results. Although the ADAPT
(The Alzheimer`s Disease Anti-inflammatory Prevention Trial) trial
was stopped early, recent results suggest that NSAIDs can help
people with early stages of AD but that prolonged treatment is
necessary to see benefit.
Dr Irene Knuesel who led this research explained, “The AD-like
changes within the brain of these mice occurred without an increase
in amyloid β (Aβ). However, in mice genetically modified to produce
the human version of Aβ, the viral-like challenge drastically
increased the amount of Aβ at precisely the sites of
inflammation-induced APP deposits. Based on the similarity between
these APP/Aβ aggregates in mice and those found in human AD, it
seems likely that chronic inflammation due to infection could be an
early event in the development of AD.
Krstic D et al. Systemic immune challenges trigger and
drive Alzheimer-like neuropathology in mice. Journal of
Neuroinflammation (in press)