Brain iron distribution and mitochondrial features in the early phases of amyloidosis in 5xFAD mouse model

As population age increases, embracing a healthy lifestyle for a healthy aging process, is more crucial than ever. Alzheimer's disease (AD) is the most prevalent form of dementia caused, among others, by the rise in age. AD reveals itself through a range of symptoms incorporating deteriorating mental abilities, changes in behaviour and loss of memory. The deposition of beta-amyloid plaques and neurofibrillary tangles plays a significant role in the pathophysiological process that leads to neural death in AD. Currently, due to a lack of total understanding of its elaborate molecular mechanisms, hindering early detection, the disease remains untreatable. In this study the murine 5xFAD model, which carries five human familial mutations for AD, is characterized in the early stages of amyloidosis, analogous to those seen in AD-pathology with the aim to define novel mechanisms and target for early detection and possible therapies. Iron metabolism and mitochondrial dysfunction are investigated in brain tissues from 5xFAD mice and human samples. Results showed that iron accumulation is an early phenomenon in AD, appearing very early, both in the hippocampus and striatum, before visible amyloid plaques could be observed. Iron dyshomeostasis contributes to neuroinflammation and oxidative stress. Indeed, we observed early astrogliosis and mitochondrial alterations. Also in human brains iron dyshomeostasis occurs in an age and gender dependent manner. These findings suggest that early iron accumulation may be an event triggering and contributing to AD pathology and brain aging, further providing new knowledge about diagnostic and therapeutic targets