ABC-AD: ABC transporters as early diagnostics and treatment marker for neurodegenerative dementias – towards a personalised medicine in dementia
ABC transporters as early diagnostics and treatment marker for neurodegenerative dementias
Currently early diagnostics and treatment of dementia is not securely available. We have discovered that ABC transporters play a fundamental role in excreting toxic peptides from the brain and that this mechanism can be used for diagnostics and treatment. It was confirmed in elderly having reduced transbarrier clearance at the blood-brain barrier.
The project focuses on deciphering genomic alterations in ABC transporter genes with respect to type of neurodegenerative / neuroinflammatoy disease, onset of disease and also possible treatment effects of ongoning treatment in the patients. Additionally, we integrate data about the circumstances of living and the progression of disease. We investigate ABC transporter loci of an excisting and clinically characterized cohort of neurodegenerative diseases in Magdeburg / Germany. Our goal is to detect changes in the genomic arrangement in the ABC transporter loci, mitochondria and binding miRNA with sporadic forms of the diseases. Since we have not been granted money for the financing of the chemicals for sequencing as applied for, we have been submitting additional grants (as suggested by HSØ) again for the sole financing of the chemicals for library generation and next-genome sequencing. Unfortunately, we did not receive funding in the recent round (note from Dec 2016) and also no additional hints why not. As we have been stating before it is essential for the project to finance the chemicals/consumables. To grant a position for research without granting the consumables is nice, but is not sufficient for projects that indeed rely on new and expensive methods, especially if a larger cohort needs to be fully analysed for statistical reasons. To overcome these caveats we have been starting with the setup of confirmation assays and as proposed by one of the reviewers before with possiblilities to check the results in model organisms. Herefore, we established also assays from primary vessel cells / endothelia and pericytes/ from humanised animals to be able to set up a method for in vitro analyses. Humanized animals enable us the directly control for a human gene function/ alteration in an animal background which is thought to be more realistic with respect to later clinical use that the sole transgene or knockout models. The availaible models represent 3 ABC human transporters and are currently checked for the right expression distribution.
Revisiting rodent models: Octodon degus as Alzheimer's disease model?
Acta Neuropathol Commun 2016 Aug 26;4(1):91. Epub 2016 aug 26
The choroid plexus in health and in disease: dialogues into and out of the brain.
Neurobiol Dis 2016 Aug 18. Epub 2016 aug 18
32nd International Austrian Winter Symposium : Zell am See, the Netherlands. 20-23 January 2016.
EJNMMI Res 2016 Apr;6(Suppl 1):32. Epub 2016 apr 18
Morphometric analysis of the cerebral expression of ATP-binding cassette transporter protein ABCB1 in chronic schizophrenia: Circumscribed deficits in the habenula.
Schizophr Res 2016 Nov;177(1-3):52-58. Epub 2016 mar 3