Citations 1
Targeted plasma proteomics uncover novel proteins associated with KIF5A -linked SPG10 and ALS spectrum disorders
Orlacchio, Antonio , Munain, Adolfo López de, Vucic, Steve , Barakat, Tahsin Stefan , Petrucelli, Leonard , Prudencio, Mercedes , Weishaupt, Jochen H., Prudencio, Mercedes , Dulski, Jarosław , Boddapati, Arun Kumar , Risi, Barbara , Iruzubieta, Pablo , Fernández‐Torrón, Roberto , Castillo‐Triviño, Tamara , Munain, Adolfo López de, Padovani, Alessandro , Kaat, Laura Donker , Landers, John E. , Weishaupt, Jochen H. , Prokop, Andreas , Filosto, Massimiliano , Wszołek, Zbigniew K. , Pant, Devesh C.
No container title available | May 2, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract KIF5A (Kinesin family member 5A) is a motor protein that functions as a key component of the axonal transport machinery. Variants in KIF5A are linked to several neurodegenerative diseases, mainly spastic paraplegia type 10 (SPG10), Charcot-Marie-Tooth disease type 2 (CMT2), and amyotrophic lateral sclerosis (ALS). These diseases share motor neuron involvement but vary significantly in clinical presentation, severity, and progression. KIF5A variants are mainly categorized into N-terminal variants associated with SPG10/CMT2 and C-terminal variants linked to ALS. This study utilized a novel multiplex NULISA targeted platform to analyze plasma proteome from KIF5A -linked SPG10, ALS patients and compared to healthy controls. Our results revealed distinct proteomic signatures, with significant alterations in proteins related to synaptic function, and inflammation. Notably, neurofilament light polypeptide, a biomarker for neurodegenerative diseases, was elevated in KIF5A ALS but not in SPG10 patients. Moreover, these findings can now be taken forward to gain mechanistic understanding of axonopathies linking to N- vs C-terminal KIF5A variants affecting both central and peripheral nervous systems.