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050 Western blot analysis of KPNA4 and its relevance to nucleocytoplasmic transport dysfunction in ALS/FTD
  1. Anna Zatorska1,
  2. Daniel Solomon2,
  3. Tibor Hortobagyi2,
  4. Frank Hirth2
  1. 1University of Southampton
  2. 2King’s College London


ALS and FTD are progressive neurodegenerative diseases, often characterised by cytoplasmic aggregation of TDP-43. Nuclear import of TDP-43 occurs via the classical pathway in which karyopherin alphas (KPNAs) act as adaptor proteins. KPNA4 has been identified as the strongest interactor of TDP-43, and karyopherins co-localise with the aberrant cytoplasmic aggregates in ALS/FTD.

This study explored how KPNA4 is affected in the spinal cord of sporadic-ALS (n=8), C9ORF72-ALS cases (n=7) as compared to control (n=6) and in the frontal cortex of sporadic-FTD (n=8), C9ORF72-FTD (n=8), and Tau-FTD (n=8) as compared to control (n=8). Quantitative western blotting was used to analyse whether KPNA4 differed between the protein samples from post-mortem tissue.

Soluble levels of KPNA4 were significantly lower in the spinal cord of sporadic-ALS patients compared to control (D=0.4321, CI= 0.124–0.7401, p=0.0086), in the frontal cortex of sporadic-FTD patients compared to control (D=0.258, 95% CI=0.065–0452, p= 0.01) and in the frontal cortex of Tau-FTD patients compared to control (D= 0.22, CI= 0.03–0.42, p= 0.022) but not in C9ORF72 ALS/FTD.

The results show a statistically significant downregulation of KPNA4 in sporadic ALS/FTD and Tau-FTD, suggesting KPNA4 could be forming insoluble aggregates or that the translation of KPNA4 mRNA may be reduced.

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