Novel insights into SORL1: unraveling the role of the fourth autosomal-dominant Alzheimer’s disease gene

2021.08.27 | Graduate School of Health

On Thursday 16 September at 15.00, Giulia Monti defends her PhD dissertation entitled "Novel insights into SORL1: unraveling the role of the fourth autosomal-dominant Alzheimer’s disease gene".

Alzheimer’s disease (AD) is a neurodegenerative disorder representing the most common form of dementia. Aetiology of AD is linked to multiple factors, and genetic studies uncovered several genes associated to disease. Among these, SORL1 encoding the sortilin-related receptor SORLA is now considered one of the main genetic determinants of AD. However, it is still unclear how specific SORL1 variants are pathologically linked to AD. A deeper comprehension of this gene and its translational product is thus key to fully understand if and how SORL1 mutations are causative of AD.

The general aim of this PhD study was to further characterize SORL1/SORLA to reveal new functional aspects that could help advancing our knowledge about its role in the pathology. This was carried out following three different approaches. First, a novel missense SORL1 variant associated with AD in an Icelandic family was characterized, focusing on its role in APP processing and SORLA shedding through the establishment of an in vitro assay. Moreover, the second aim was to describe a novel human specific SORL1 transcript produced by alternative splicing in both healthy and AD brain. Finally, the spatio-temporal characterization of SORL1/SORLA was examined in the postnatal mouse retina taking advantage of a SORLA-deficient mouse model and a variety of molecular biology techniques.   

The summary is written by the PhD student.   

The defence is public and takes place online via Zoom.  Please read the attached press release for more information.

Contact:

PhD student Giulia Monti

Mail: gm@biomed.au.dk 

Phone: (+45) 50218716

Read full press release