The deposition of amyloid-beta (Ab) in the walls of cerebral vessels as cerebral amyloid angiopathy (CAA) is a key feature of Alzheimer’s disease (AD). There is currently no efficient treatment for AD or CAA and with the increase in life expectancy, the socio-economic burden of dementia is set to increase dramatically if a cure is not found. We have demonstrated that Ab is eliminated along the basement membranes of capillaries and arteries as intramural periarterial drainage (IPAD) and this fails with increasing age leading to CAA. Clusterin (CLU) is elevated in the cerebrospinal fluid in AD and in the cerebral vessels of CAA. Our experimental studies show that in the absence of CLU the CAA worsens. Here, through a novel collaboration between the PI based in the UK and researchers in Targu Mures Romania, as well as a key collaborator in Australia who will synthesise CLU, using state of the art in vivo techniques and confocal microscopy we aim to test the hypotheses that

                 1. The absence of CLU results in failure of IPAD of Ab;

                  2. Recombinant CLU prevents/ameliorates CAA in a model of AD.

Our results are essential in the understanding of the pathophysiology of the factors that facilitate IPAD and will pave the way for novel efficient interventions to prevent or treat CAA and Alzheimer’s disease.

Raport științific și tehnic – Clusterina, un nou agent terapeutic util în clearance-ul amiloidului vascular (PN-III-P4-ID-PCE2020-1622)

Scientific report – Clusterin as a new therapeutic target to improve clearance of vascular amyloid (PN-III-P4-ID-PCE2020-1622)

Raport științific  – Clusterina, un nou agent terapeutic util în clearance-ul amiloidului vascular (PN-III-P4-ID-PCE2020-1622)

Executive summary

This project is supported by a grant of the Romanian Ministry of Education and Research, CNCS – UEFISCDI, project number PN-III-P4-ID-PCE-2020-1622, within PNCDI III