Dottoressa di ricerca

ciclo: XXXIII


This thesis's core concept is that translational neuroimaging biomarkers are suitable candidates to investigate the differential effects of transgenic configurations on neuroanatomy in AD animal models; and that multimodal neuroimaging may play an important role in the improved understanding of the disease mechanism and continuing development and refinement of diagnostic strategies. (i) Within the first research project, we explored the neuroanatomical trajectories in two AD animal models. With a longitudinal design and deformation-based morphometry, we sought to determine how two different transgene configurations (one pure APP and another one - a triple transgenic (TG) line expressing both APP and tau mutations) affect mouse brains. The main findings of this study were: (i) atrophic phenotype is linked to tau expression; (ii) APP model of AD is rather a model of amyloid deposition combined with developmental phenotype than a model of neurodegeneration. Furthermore, we investigated a sex effect and found that the TG genotype has a more detrimental impact on neuroanatomical remodeling in female triple transgenic mice than in males. (ii) Next, we investigated covariance patterns between indices obtained with the resting state (rs) EEG and structural MRI on the same participants with AD dementia and normal elderly. More specifically, we explored how cortical thickness covary with the amplitude of cortical sources of rsEEG rhythms with a partial least squares analysis, as it is well suited to reveal patterns of covariation in data. The results of this study revealed that rsEEG slowing occurring in AD is related to network-wide atrophy of cortical areas. Furthermore, our results suggest that in AD reduced power of occipital cortical sources have a stronger relationship to the network-wide atrophy in comparison to other rsEEG features. (iii) And last but not least, we evaluated the combined performance of different EEG biomarkers in detecting AD. The results showed that EEG biomarkers may be used in clinical studies performed in patients with AD in response to the need for gatekeeper screening tests of large groups of the aging population. These results improve understanding of translational sMRI and rsEEG biomarkers towards future applications as screening tools in AD patients at the prodromal stage of amnestic mild cognitive impairment (aMCI) and dementia as well as in the preclinical studies along the pathway of drug discovery in transgenic AD mouse models.

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