Yasmine Iacone (Presenter)
University of Gothenburg
Authorship: Yasmine Iacone (1), Ibrahim Kaya (1), Wojciech Michno (1), Dimitri Brinet (1) and Jörg Hanrieder 1,2,3
(1) University of Gothenburg, Gothenburg, Sweden (2) Chalmers University of Technology, Gothenburg, Sweden; (3) University College London
| Short Abstract Alzheimers disease is the most common neurodegenerative disease affecting 1 in 8 over the age of 65. Genetic predisposition with the apolipoprotein E (APOE) e4 allele, a lipid transporter protein, was identified as the major risk factor to develop sporadic AD, implicating a prominent role for lipids in AD pathogenesis. This highlights the need for further investigation of chemical changes in brain lipid species in AD pathology. Here, MALDI imaging mass spectrometry has been used to determine lipids mass profile around plaques of post mortem human cortical brain from AD patients. In detail, sublimation with 1,5 diaminonaphtalene (1,5 DAN) was used for high resolution imaging of lipid species followed by amyloid staining on the same tissue. The data show distinct lipid localisations, including ganglioside species that were correlated to AD pathology. |
Long Abstract
Alzheimer’s disease (AD) is one of the most common later-onset neurodegenerative disorders. The pathological hallmarks of the disease comprehend abnormal protein aggregation of amyloid beta peptide into extracellular compact plaques, and the hyperphosphorilation of intraneuronal tau protein.1 Evidences suggest that lipids are as well determinant factors for the progression of the disease. Neuronal lipid species they are linked to several biochemical mechanisms involved in brain functions.2 Moreover, genetic predisposition with the apolipoprotein E (APOE) e4 allele, a lipid transporter protein, was identified as the major risk factor to develop sporadic AD, implicating a prominent role for lipids in AD pathogenesis. This requires therefore further insights in pathological and chemical changes of brain lipid species and there association with AD pathology, including amyloid plaque formation.
Mass spectrometry imaging is one of the emerging techniques for the localization of different structures in biological tissues and has been fully employed to chemically and structurally characterized different lipids profiles.
The aim of this study was therefore to employ MALDI imaging for elucidating amyloid plaque associated lipid species in human brain tissue.
Methods
In this study, we used sublimation of 1,5-diaminonaphtalene (1,5-DAN) as MALDI matrix that yielded high quality lipid signals on cortical human brain sections. The technique provided high spatial resolution (down to 10µm). This was followed by subsequent amyloid staining on the same tissue section.
Results
We report herein the lipids mass profile around Aβ plaques in post mortem human cortical brain regions that were correlated to respective changes in AD pathology. The data show distinct localisation of ganglioside species to the plaques further supporting the relevance of gangliosides in AD pathology.
Conclusion
This is the first study on demonstrating imaging MS based identification of spatial lipid changes associated with amyloid pathology underlying AD pathogenesis. The results suggest a prominent functional role of e.g. ganglioside metabolism in AD pathology and further highlight the potential of imaging MS in studying neurodegenerative mechanisms comprehensively in situ.
References & Acknowledgements:
(1) Blennow, K. et al. Alzheimer’s disease, Lancet, 2006, 368:387-403
(2) Di Paolo, G.; Kim, T.-W., Linking lipids to Alzheimer's disease: cholesterol and beyond. Nature Reviews Neuroscience 2011, 12 (5), 284-296
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