In vivo assessment of glymphatic clearance by DCE-MRI as potential prognostic biomarker of Alzheimer's disease
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1
University of Antwerp, Belgium
The glymphatic system (GS) is a recently identified glial-dependent brain clearance route with an implicated fundamental role in the drainage of solutes and waste proteins- such as amyloid-β and hyperphosphorylated tau (p-tau). The efficacy of the GS decreases during aging, possibly leading to an accumulation of waste proteins. This decreased glymphatic-drainage is postulated to play a key role in the initiation and progression of neurodegenerative disorders, including Alzheimer disease (AD). Therefore, understanding its function in neurodegenerative disorders is essential for the development of new diagnostic biomarkers and therapies.
To investigate how GS function is altered in AD, dynamic contrast-enhanced MRI (DCE-MRI) was performed to visualize, in vivo, the ‘glymphatic flow’ in two rodent models of AD. DCE-MRI was acquired in a mouse model with inducible amyloid expression, TetO-APPSweInd, to investigate the effect of amyloid on GS function. Furthermore, DCE-MRI was performed in a translational rat model (TgF344-AD), which exhibits both amyloid and tau pathology, to assess changes in clearance due to the AD pathology. In both animal models, experiments were performed when AD pathology was already advanced.
Our results demonstrate that clearance patterns are altered in both rodent models of AD. The amyloidosis mouse model displayed altered distribution patterns in the cortex, a region severely affected by amyloid plaques. In the TgF344-AD rat model, altered glymphatic clearance is observed in the thalamus, striatum, olfactory bulb and cortex, regions also affected by amyloid and tau pathology.
To conclude, changes in efficacy and function of the GS are observed in rodent models of AD and these changes coincide with the presence of pathological hallmarks of AD. Future research will focus on early changes is glymphatic clearance in AD models.
Acknowledgements
Bio-Imaging lab, university of Antwerp
Keywords:
Alzheime´s Disease,
glymphatic clearance,
MRI,
Neurodegenaration,
Dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI),
Glymphatic system
Conference:
13th National Congress of the Belgian Society for Neuroscience , Brussels, Belgium, 24 May - 24 May, 2019.
Presentation Type:
Poster presentation
Topic:
Behavioral/Systems Neuroscience
Citation:
Van Den Berg
M,
Keliris
A,
Ben-Nejma
I,
Verhoye
M,
Keliris
G and
Van Der Linden
A
(2019). In vivo assessment of glymphatic clearance by DCE-MRI as potential prognostic biomarker of Alzheimer's disease.
Front. Neurosci.
Conference Abstract:
13th National Congress of the Belgian Society for Neuroscience .
doi: 10.3389/conf.fnins.2019.96.00041
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Received:
25 Apr 2019;
Published Online:
27 Sep 2019.
*
Correspondence:
PhD. Monica Van Den Berg, University of Antwerp, Antwerp, Belgium, monica.vandenberg@uantwerpen.be