The ivBM-4PAP project aims to develop a fast-scan Brillouin Microscope capable of sub-millisecond acquisition time to be suitable for In-Vivo measurements in cells and tissues, applicable to the field of biomedicine. This represents a major breakthrough in the field of microscopy since the long acquisition time of the today standard techniques has limited their use only to fixed samples. Thus, the ivBM will allow the measurement of the dynamic changes of mechanical properties of sub-cellular structures in living cells in real time. This will be extremely relevant to uncover the protein aggregates and the pathophysiological mechanism of different neurodegenerative diseases. Among them, within this proposal, we aim to shed light on the mechanism driving the onset and the progression of frontotemporal dementia (FTD), the most common cause of dementia in younger people with a devastating prognosis and no effective treatment. Indeed, the poor translation of findings obtained from animal models to humans has contributed for the yet poorly understood disease mechanism and thereby for the failure rate in drug development. Hence, in this proposal, the UC partner will provide the consortium with in-vitro models (iPSCs and patient-derived brain organoids), that better address the specific neuropathological features of FTD patients. Also, to detect early disease phases, we will model genetic (GRN and C9orf72) mediated forms of FTD, where at-risk individuals, still asymptomatic, can be assessed prior to clinical conversion. These models will be used to test ivBM, performance in terms of reliability, spatial resolution and acquisition time. Moreover, ivBM will be used to assess the mechanical properties of the existing structures, their nature, changes in their mechanical properties and their relationship with FTD. Indeed, applying ivBM to this protein aggregation-based pathology could increase our capability for an early detection, improving patient’s prognosis and management