A Preliminary Study of Cu Exposure Effects upon Alzheimer’s Amyloid Pathology
Alexander Pilozzi,
Zhanyang Yu,
Isabel Carreras,
Kerry Cormier,
Dean Hartley,
Jack Rogers,
Alpaslan Dedeoglu,
Xudong Huang
Affiliations
Alexander Pilozzi
Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
Zhanyang Yu
Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
Isabel Carreras
Department of Veterans Affairs, VA Medical Center, Bedford, MA 01730, USA
Kerry Cormier
Department of Veterans Affairs, VA Medical Center, Bedford, MA 01730, USA
Dean Hartley
Autism Speaks, Chicago, IL 60659, USA
Jack Rogers
Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
Alpaslan Dedeoglu
Department of Veterans Affairs, VA Medical Center, Bedford, MA 01730, USA
Xudong Huang
Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
A large body of evidence indicates that dysregulation of cerebral biometals (Fe, Cu, Zn) and their interactions with amyloid precursor protein (APP) and Aβ amyloid may contribute to the Alzheimer’s disease (AD) Aβ amyloid pathology. However, the molecular underpinnings associated with the interactions are still not fully understood. Herein we have further validated the exacerbation of Aβ oligomerization by Cu and H2O2 in vitro. We have also reported that Cu enhanced APP translations via its 5′ untranslated region (5′UTR) of mRNA in SH-SY5Y cells, and increased Aβ amyloidosis and expression of associated pro-inflammatory cytokines such as MCP-5 in Alzheimer’s APP/PS1 doubly transgenic mice. This preliminary study may further unravel the pathogenic role of Cu in Alzheimer’s Aβ amyloid pathogenesis, warranting further investigation.
