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Eva Zerovnik, Natasa Kopitar Jerala and Robert Layfield
Early diagnosis and efficient treatment for sporadic Alzheimer’s disease (AD) are urgently needed as the condition becomes an increasing burden within aging societies. We collected recent data on the progress towards effective treatments of AD, from targeting Aβ aggregation, passive immunization with anti-Aβ antibodies, fighting acute and chronic inflammation, modulating autophagy to balancing metals ions. We argue that from successful model studies and pre-clinical trials, insights into the critical pathogenic mechanisms at the molecular and cellular levels are confirmed. They in one way or another seem to support the modified amyloid cascade hypothesis, in which Aβ oligomers are believed to impair intracellular membranes, possibly resulting in mitochondrial and lysosomal dysfunctions that may lead to oxidative stress and impairment in protein clearance by autophagy, respectively. In accordance, chronic inflammation due to activation of microglia, is also consistently observed in AD brains.