The inflammatory Cerebral Amyloid Angiopathy and Alzheimer’s disease Biomarkers International Network (iCAβ) initiative

AD will become a public health crisis, with significant impact on the public health finances within few years, if we will not been able to find an effective treatment. In fact, AD represents the most common cause of dementia and an increasing public health priority, whit more than 5 million of patients only in the US and with an expected increase to 13 million in 2050, resulting in a heavy personal and financial toll both for patients and family caregivers. Consistently, 3 new World-Wide DMT clinical trials are ongoing: the A4 trial in asymptomatic AD; the DIAN study in genetically defined AD; and the API initiative in the Colombian PSEN1 kindred. However, the previously reported adverse events of these DMT have negatively affected the rapid and safe discovery of an efficient cure for this devastating disease. It results quite clear that without effective biomarkers for the monitor of these abnormal events, it will be possible to incur in the same side effects previously emerged, with further serious and unacceptable delays in finding a cure for this devastating disease. Notably, the first phase I immunotherapeutic (ponezumab) trial for sporadic CAA has recently been launched. Keeping in mind these priorities, the iCAβ International Network aims to contribute to an emerging issue of public health and, at the same time, of great biological importance. A better comprehension of the CAA-related consequences of high autoantibody concentration will mark a significant advance both for the identification of biomarkers for CAA-ri and for the current ongoing clinical trials in AD, opening also to a new scenario for the therapy of CAA. Our novel ultra-sensitive test for the detection of auto-antibodies against Aβ in the CSF, can reveal extremely helpful in the prevention and monitor of the side effects of clinical trials. More importantly, a direct clinical application will finally involve patients with suspected CAA-ri, where an invasive and expensive procedure such as brain biopsy is often still needed. The validation of the test and the related anti-Aβ autoantibody cut-offs, in association with the proper clinical and MRI features, will represent a valid alternative to the current more expensive and invasive techniques for the diagnosis of CAA-ri and the ARIA-like events occurring during AD clinical trials, with relevant impact on the National Health System.