Abstract:
The mechanisms underlying the pathogenesis of Alzheimer’s disease (AD) have
long been studied, yet they remain poorly understood. Recent developments in the field
of AD research established a role for trace metal homeostasis in AD pathogenesis.
Additionally, inflammatory signaling pathways have been implicated in AD, and many of
these pathways contain metal binding proteins. The present study will build on previous
work in our lab, and focus on the role of dietary zinc and copper, as well as brain
inflammation and oxidative stress, in an early onset model of AD. Previous work in our
lab has found that excess dietary zinc can lead to copper deficiency and cause behavioral
impairments in mice and rats. We have also found that increased dietary zinc leads to
increased levels of pro-inflammatory cytokines IL-1β, and TNF-α in an AD mouse
model. This study used wildtype (WT) control, and transgenic (Tg) mice expressing one
copy of the human amyloid precursor protein mutation (hAPP), to examine the
relationship between dietary zinc and copper on brain inflammation and oxidative stress in AD. Dietary manipulations included: copper deficient diet + lab water (Cu- animals),
zinc enhanced water + copper control diet (Zn+ animals), and copper control diet + lab
water (CC animals). To measure inflammation this study examined Tumor Necrosis
Factor-alpha (TNF-α), a proinflammatory cytokine thought to be a key initiator/regulator
of the immune response. This study also examined levels of Superoxide Dismutase 1
(SOD-1), to gain insight into the role of oxidative stress in AD, as SOD- is delicately
maintained by zinc and copper levels. All biomarkers were evaluated by Western blot.
