KIF5A and KLC1 expression in Alzheimer’s disease: relationship and genetic influences
Open Access
- 19 February 2019
- journal article
- Published by F1000 Research Ltd in AMRC Open Research
Abstract
Background: Early disturbances in axonal transport, before the onset of gross neuropathology, occur in a spectrum of neurodegenerative diseases including Alzheimer’s disease. Kinesin superfamily motor proteins (KIFs) are responsible for anterograde protein transport within the axon of various cellular cargoes, including synaptic and structural proteins. Dysregulated KIF expression has been associated with AD pathology and genetic polymorphisms within kinesin-light chain-1 (KLC1) have been linked to AD susceptibility. We examined the expression of KLC1 in AD, in relation to that of the KLC1 motor complex (KIF5A) and to susceptibility genotypes. Methods: We analysed KLC1 and KIF5A gene and protein expression in midfrontal cortex from 47 AD and 39 control brains. Results: We found that gene expression of both KIF5A and KLC1 increased with Braak tangle stage (0-II vs III-IV and V-VI) but was not associated with significant change at the protein level. We found no effect of KLC1 SNPs on KIF5A or KLC1 expression but KIF5A SNPs that had previously been linked to susceptibility in multiple sclerosis were associated with reduced KIF5A mRNA expression in AD cortex. Conclusions: The findings raise the possibility that genetic polymorphisms within the KIF5A gene locus could contribute to disturbances of axonal transport, neuronal connectivity and function across a spectrum of neurological conditions, including AD.Keywords
Funding Information
- BRACE
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