AUTHOR=Katzeff Jared S. , Lok Hiu Chuen , Bhatia Surabhi , Fu YuHong , Halliday Glenda M. , Kim Woojin Scott TITLE=ATP-binding cassette transporter expression is widely dysregulated in frontotemporal dementia with TDP-43 inclusions JOURNAL=Frontiers in Molecular Neuroscience VOLUME=15 YEAR=2022 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2022.1043127 DOI=10.3389/fnmol.2022.1043127 ISSN=1662-5099 ABSTRACT=

The human brain is highly enriched in lipids and increasing evidence indicates that dysregulation of lipids in the brain is associated with neurodegeneration. ATP-binding cassette subfamily A (ABCA) transporters control the movement of lipids across cellular membranes and are implicated in a number of neurodegenerative diseases. However, very little is known about the role of ABCA transporters in frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), which is a common form of younger-onset dementia. We therefore undertook a comprehensive analysis of the expression of ABCA transporters (ABCA1–13) in five key brain regions (amygdala, inferior temporal cortex, superior frontal cortex, cerebellum and parietal cortex) in FTLD-TDP and controls. We found that the expression of ABCA2, ABCA3, ABCA4, ABCA7, ABCA9, ABCA10 and ABCA13 was significantly altered in FTLD-TDP in a region-specific manner. In addition, the expression of ABCA transporters correlated specifically to different neural markers and TARDBP. These results suggest substantial dysregulation of ABCA transporters and lipid metabolism in FTLD-TDP and these changes are associated with neuroinflammation.