Alzheimer’s disease (AD) is a challenging disease to diagnose and treat. Recent studies have shown that
innate immunity and inflammation play key roles in the pathogenesis of AD. Myeloperoxidase (MPO) is
a highly damaging substance secreted abundantly in inflammatory conditions by activated microglia and
astrocytes. MPO has been associated with beta-amyloid in both AD and animal models. MPO is more
abundant in female AD patients and those showing cognitive decline, and is also strongly implicated in
cardiovascular diseases, which can exacerbate AD. Our preliminary data showed that MPO activity can be
inhibited in animals and doing so improved outcome in murine models of neuroinflammatory diseases
and AD. As MPO is a key modulator of inflammation, and
neuroinflammation is intimately associated
with beta-amyloid in animal models of AD and in human AD, the proposed project aims to establish MPO
as a biomarker for early neuroinflammation and damage, and MPO inhibition as a new therapeutic
strategy to decrease damage in AD. Given that neuroinflammation is an early event, MPO inhibition
could also be useful for early intervention to prevent progression of disease at the first signs of cognitive
decline prior to the onset of dementia in at-risk patients. Another key aspect of this proposal is the use of
novel multimodal
in vivo molecular imaging technologies to monitor the status of both MPO and betaamyloid
noninvasively and longitudinally to assess treatment efficacy.
