Dysregulation of Neuronal Iron Homeostasis as an Alternative Unifying Effect of Mutations Causing Familial Alzheimer’s Disease

• DOI: 10.3389/fnins.2018.00533
• Publication Date: 2018-08-13T08:56:13Z
• Authors: Amanda L. Lumsden; Jack T. Rogers; Shohreh Majd; Morgan Newman; Greg T. Sutherland; Giuseppe Verdile; Michael Lardelli
• Keywords: PSEN1; Amyloid (mycology)

The overwhelming majority of dominant mutations causing early onset familial Alzheimer's disease (EOfAD) occur in only three genes, PSEN1, PSEN2, and APP. An effect-in-common these is alteration production the APP-derived peptide, amyloid β (Aβ). It this key fact that underlies authority Amyloid Hypothesis has informed research for over two decades. Any challenge to must offer an alternative explanation relationship between PSEN genes In paper, we explore one possible - dysregulation cellular iron homeostasis as a common effect EOfAD genes. This idea attractive since it provides clear connections major characteristics such dysfunctional mitochondria, vascular risk factors/hypoxia, energy metabolism, inflammation. We combine our ideas with observations by others describe "Stress Threshold Change State" model may begin explain existence both late sporadic (LOsAD) forms disease. Directing investigate role be profitable way forward struggle understand form dementia.