Fulvio Da Re

Fulvio Da Re was born on August 29, 1986, he gained his Medical Degree in 2011 at the University of Milan-Bicocca, where he also became a Neuroscience PhD Student in November 2016, and a Neurologist in 2017. His MD thesis about the possible role of the Nanoparticles in Alzheimer’s Disease, pursued in the laboratory of Neurobiology of the same University, was awarded from SinDEM and Italian Alzheimer Federation, due to innovative idea.

During the residency he progressively abandoned the preclinical research in favour of the clinical one, for which he has been conducting research in the “Frontotemporal Degeneration Center – University of Pennsylvania” for eight months, under the direction of Dr. Murray Grossman.

RESEARCH PROJECT

Amnestic and non-amnestic phenotypes of Alzheimer’s disease: an MRI-based phasing analysis

  • Track: Neuroscienze cliniche
  • Tutor: Carlo Ferrarese

Typical amnestic Alzheimer’s disease (AD) presents with memory difficulty, and pathology is first seen in the medial temporal lobe (MTL). Disease then spreads to cortex as language, visuospatial, and executive difficulties emerge. In contrast, these cognitive domains are the first impaired in non-­amnestic AD. Pathologically, non-amnestic AD patients have relative sparing of MTL and selective distribution of pathology in the cortex. However, the temporal progression of disease is unclear.

This project will investigate: the possible differences in brain areas of onset among typical and the atypical variants of AD; the different progression pathways of the disease throughout the brain depending on the different types, analysing both the GM and the WM; the neuropsychological assessments most correlated to the GM Density (GMD) for each variant and for the whole group too. Hence, the final goal of this project is to obtain a deeper understanding of the pathophysiology of AD onset  and to provide more defined inclusion/exclusion criteria for the atypical variants. Moreover, a deeper knowledge of AD spread pathways could provide possible target for future specific disease-modifying therapies, able to stop the disease progression.

To investigate my hypothesis, I will analyze the onset areas and the progression pathways using both cross-sectional and longitudinal 3 Tesla MRI (structural and DTI) data. An appropriate sample size will be determined, based on desired statistical power. All T1-weighted images will be processed in a specific software (SPM) and normalized with a specific disease template, in order to obtain z-score images, reflecting deviation from healthy controls. In a post-processing phase different staging maps will be created; I will highlight for each variant the brain areas with a z-score images of <- 1.5 as cut-off. Starting from the idea that the more an area is involved, the earlier it would have been injured (like assumed by other authors, like Ossenkoppele R et al. Hum Brain Mapp 2015) it will be possible to create a chronological pattern of atrophy diffusion. I could subsequently confirm that this model is correct with a longitudinal study using a subset of samples with 2 or more images in different timepoints: for each variant will be performed a regression analysis with z-scores images, disease duration at time of MRIs (2+) and clinical severity (neuropsychological assessment scores).  Finally, it will be interesting to correlate the z-score images of the different variants with the neuropsychological assessments, looking for scales able to reflect the severity of the atrophy.  The last phase of the project will focus on the WM: using a process similar to the above one used for the GMD, I could study the pathways of disease progression. Substituting the GMD values with the DTI parameters, it would be possible to create staging maps for the WM integrity too.

The leading hypothesis of the present project is that atypical AD have different brain areas of degeneration onset, which are respectively linked to the main impaired cognitive domain, and various spreading patterns. Particularly I expect to find a specific spread pathway, starting from the brain area of onset, for each of the variant through the association fibers (as suggested in the Wallerian Degeneration model).

ABROAD STAGE

In the context of the international mobility project Exchange Extra-UE set up by University of Milano-Bicocca for internships outside Europe, I started working on my project at FTD Center of University of Pennsylvania, in Philadelphia, under the direction of Dr. Murray Grossman. I’m going to go back there for a second period, from August 2017 to December 2017, to pursue my research activities.

RECENT PUBLICATIONS AND CONGRESSES

Publications

Congresses

  • I’m going to present my project as an oral communication in July 2017, in London, at Alzheimer’s Imaging Consortium (AIC), preconference of Alzheimer Association International Conference (AAIC), where I’m going to present the study with a poster instead.
  • I’m going to present the project agai , considering new updates, in November 2017, talking in a nanosymposium at Society for Neuroscience (SfN).

FURTHER INFO

To get further details and the full pub list, go to:

Elisabetta Donzelli
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