Metal Exposure and Alzheimer’s Pathophysiology

Xudong Huang

doi:10.4172/2167-0501.1000e156

Abstract

1Department of Psychiatry, Neurochemistry Laboratory, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA 2Department of Neurology, Advanced Tissue Resource Center, Harvard NeuroDiscovery Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA 3X-ray Science Division, Argonne National Laboratory, Argonne, IL 60439, USA 4Translational Neurotherapeutics Laboratory, VA Boston Healthcare System and Department of Neurology, Boston University Alzheimer’s Disease Center, Boston University School of Medicine, Boston, MA 02130, USA

Highlights

Alzheimer’s disease (AD) is the most common form of senile dementia that affects 5.4 million Americans, and at least $183 billion was spent in 2011 on management of AD and related dementia patients
The neuropathology of AD is characterized by the accumulation of insoluble Aβ amyloid peptides, neurofibrillary tangles (NFTs, the misfolded microtubuleassociated tau protein), neuropil threads, and neuronal losses in postmortem AD brains [3,4]
a much larger metalloproteinamyloid precursor protein (APP) cleavage by α-secretase generates neurotrophic APP(s), while its synergistic cleavage by βand γ-secretases leads to production of a pool of Aβ peptides with carboxyl-terminal heterogeneity [9]: Aβ1-40 (40 amino acid residues) is the major soluble Aβ species, which is found in the CSF at low nanomolar concentrations [10]; Aβ1-42 (42 residues) is a minor Aβ species, but more neurotoxic than Aβ1-40, and is heavily enriched in

Summary

Introduction

Alzheimer’s disease (AD) is the most common form of senile dementia that affects 5.4 million Americans, and at least $183 billion was spent in 2011 on management of AD and related dementia patients. The amyloid cascade hypothesis remains to be fully validated as AD is a polygenic and multifactorial complex disease [11]. Exact AD etipathology remains to be fully elucidated, brain Aβ amyloidosis is still considered to be one of AD neuropathological hallmarks.

Results

Conclusion