The Neurodegenerative Elderly Syndrome (NES) hypothesis: Alzheimer and Parkinson are two faces of the same disease

Increasing evidence suggests that Alzheimer’s disease (AD) and Parkinson’s disease (PD) share monoamine and alpha-synuclein (αSyn) dysfunctions, often beginning years before clinical manifestations onset. The triggers for these impairments and the causes leading these early neurodegenerative processes to become AD or PD remain unclear. We address these issues by proposing a radically new perspective to frame AD and PD: they are different manifestations of one only disease we call “Neurodegenerative Elderly Syndrome (NES)”. NES goes through three phases. The seeding stage, which starts years before clinical signs, and where the part of the brain-body affected by the initial αSyn and monoamine dysfunctions, influences the future possible progression of NES towards PD or AD. The compensatory stage, where the clinical symptoms are still silent thanks to compensatory mechanisms keeping monoamine concentrations homeostasis. The bifurcation stage, where NES becomes AD or PD. We present recent literature supporting NES and discuss how this hypothesis could radically change the comprehension of AD and PD comorbidities and the design of novel system-level diagnostic and therapeutic actions.