Fulvio Da Re

Fulvio Da Re

Fulvio Da Re è nato il 29 agosto 1986, ha conseguito il titolo di Dottore in Medicina e Chirurgia nel 2011 presso l’Università degli Studi di Milano-Bicocca e quindi quello di Medico Specialista in Neurologia nel 2017 presso lo stesso ateneo, dove da novembre 2016 è anche un dottorando in Neuroscienze.
La sua tesi di Medicina e Chirurgia sul possibile uso delle nanoparticelle nella Malattia d’Alzheimer, condotto presso il laboratorio di Neurobiologia della stessa Università, ha vinto un premio come idea innovativa da parte della SinDEM e della Federazione Italiana Alzheimer.
Durante gli anni di specialità ha gradualmente abbandonato la ricerca preclinica in favore di quella clinica, per la quale da otto mesi svolge attività di ricerca presso il “Frontotemporal Degeneration Center – University of Pennsylvania”, sotto la guida del Dr. Murray Grossman.

PROGETTO DI RICERCA

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

  • Curriculum: 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).

PERIODI ALL’ESTERO

Nel contesto del progetto di mobilità internazionale Exchange Extra-UE previsto da Bicocca per esperienze al di fuori dell’Europa, ho iniziato a lavorare al progetto all’FTD Center dell’Università della Pennsylvania, con sede a Filadelfia, sotto la guida del Dr. Murray Grossman. Svolgerò in tal sede un secondo periodo, da agosto 2017 a dicembre dello stesso anno, per proseguire l’attività di ricerca.

PUBBLICAZIONI E CONGRESSI RECENTI

Pubblicazioni

Congressi

  • A Luglio 2017 presenterò il progetto come comunicazione orale a Londra all’Alzheimer’s Imaging Consortium (AIC), preconferenza dell’Alzheimer Association International Conference (AAIC), dove invece presenterò il lavoro con un poster.
  • A Novembre 2017 presenterò nuovamente il progetto, con i nuovi aggiornamenti, parlando durante un nanosymposium alla Society for Neuroscience (SfN).

ALTRE INFO

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Elisabetta Donzelli
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