Fabrizio Piazza, a pharmaceutical biotechnologist, doctor of molecular and translational medicine and professor of Technical Sciences of Laboratory Medicine in the University of Milan-Bicocca’s Department of Medicine and Surgery, has been awarded the Alzheimer’s Association Research Grant (AARG), winning $200,000 in funding through the grant programme promoted by the Alzheimer’s Association, the world’s leading organisation in the field of voluntary work, care, support and research on Alzheimer’s, established in 1980 in the United States.
Professor Piazza was the only scientist in Italy to receive this competitive funding in the call launched last autumn and promoted by the American association to support scientific research in understanding Alzheimer’s disease, identifying new therapeutic strategies, improving care for people with dementia, deepening knowledge of brain health and preventing neurodegenerative diseases.
Fabrizio Piazza, 44, from Lecco, directs the Laboratory of Translational Research and Biomarkers for Alzheimer’s Disease and Cerebral Amyloid Angiopathy at Bicocca’s Department of Medicine and Surgery, located in the University’s Monza biomedical campus. Professor Piazza’s laboratory is also the coordinating centre of the iCAB International Longitudinal Cohort Registry, the largest consortium bringing together the world’s leading centres of excellence focused on the study of cerebral amyloid angiopathy (CAA) and amyloid-related imaging abnormalities (ARIA).
Supporting the best research presented by young researchers and promoting their independent scientific careers has always been the main goal of the Alzheimer’s Association. This is the second award that Fabrizio Piazza has received from the American organisation in just five years. “Thanks to this new funding from the Alzheimer’s Association,” comments the University of Milan-Bicocca professor, “we will be able to further strengthen the University of Milan-Bicocca’s national and international leadership in the field of precision medicine and advanced diagnostics through the use of innovative biomarkers for these diseases that are still poorly understood and therefore often prone to incorrect and untimely diagnosis, forcing patients to make continuous ‘journeys of hope’.” Over the past decade, we have heavily invested in the establishment of the iCAB Network, which is now proving to be a unique resource for addressing new research challenges in the field of biomarkers. Our recent evidence, published in the most prestigious scientific journals in the field, suggests that ARIA adverse events associated with monoclonal antibody immunotherapy for Alzheimer’s disease represent the iatrogenic manifestation – i.e. exacerbated by the drug – of autoimmune and inflammatory phenomena that occur spontaneously in cerebral amyloid inflammatory angiopathy (CAA-ri), a rare autoimmune encephalopathy mediated by autoantibodies directed against the amyloid beta protein. This ‘toxic’ protein is believed to be the basis of Alzheimer’s disease and is the main therapeutic target of immunotherapeutic drugs (monoclonal antibodies) in clinical trials.”
“Our hypothesis is that although these drugs have clearly demonstrated a ‘disease-modifying’ action, i.e. the removal of the amyloid protein from brain tissue, if not appropriately modulated and customised in their dosage they could trigger potentially damaging mechanisms at the level of cerebral vessels, such as cerebral inflammatory oedema (CAA-ri) which, if not diagnosed and treated in a timely manner, leads to the subsequent development of cerebral microhaemorrhages (CAA). To date, CAA, CAA-ri and ARIA are exclusively diagnosed by means of rigorous nuclear magnetic resonance imaging (MRI) protocols. The fact that ARIA still occurs in more than 35% of Alzheimer’s patients treated with immunotherapy clearly indicates that MRI alone is not sufficiently sensitive and specific for an early diagnosis of ARIA and for monitoring the response to treatment. Moreover, the biological significance and long-term effects of ARIAs are still largely unknown.”
“In this context,” Fabrizio Piazza continues, “the AARG Grant will focus on the definition of a diagnostic algorithm based on ultra-sensitive biomarkers assessed through the use of innovative technologies in biological fluids, in association with the latest clinical and radiological criteria for the diagnosis of CAA and CAA-ri.”
“Over the next three years, our research project, entitled ‘UNIMIB-ARIA Toolkit’,” Piazza continues, “aims to identify and validate a panel of biomarkers capable, on the one hand, of providing an increasingly early and accurate diagnosis of CAA-ri and ARIA, and, on the other, of better understanding the immune, inflammatory and cerebrovascular mechanisms associated with anti-amyloid antibodies in patients with neurodegenerative diseases such as CAA and Alzheimer’s.”