Nuclear Pore Complex Mislocalization in Hippocampal Neurons in Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder characterized clinically by memory loss, confusion and pathologically by the presence of amyloid beta plaques and neurofibrillary tangles. Even though anti-amyloid vaccination clinical trials have removed amyloid plaques, clinical efficacy has not been achieved during the early phases of AD suggesting that other mechanism play a role in the dementia associated with AD. Mutations in nucleoporin genes have been linked to various human diseases including neurological, nephrotic, cardiac, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). A recent study found mislocalization of NUP98 and NUP62 in the cytoplasm of human hippocampal neurons in AD (Eftekharzadeh et al., 2019). These NUP’s were associated with phosphorylated-tau, suggesting the depletion of nucleoporins from the nuclear envelope potentially having a direct interaction with phospho-tau. The present study investigated the three differentially expressed NUPs (NUP-214, -93, -153) from different parts of the NPC (cytoplasmic filaments, inner ring structure, nuclear basket) using immunohistochemistry and immunoblotting procedures. This investigation represents one of the first attempts to categorize differential structural changes throughout the NPC in AD.