Functional Interaction between Amyloid-β Precursor Protein and Peripherin Neurofilaments: A Shared Pathway Leading to Alzheimer's Disease and Amyotrophic Lateral Sclerosis?

The pathology of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder affecting motor neurons, comprises aberrant accumulations of neurofilaments; mutations in the peripherin subunit of neurofilaments have been identified in some forms of ALS. Recently, the amyloid-β precursor protein (APP), a key element for the pathology of Alzheimer's disease (AD), was linked to ALS. Here, we provide evidence that the generation of the N-terminal fragment of APP, sAPP, relies on peripherin neurofilaments. This finding could relate to a novel molecular mechanism dysregulated in ALS and/or AD.