Protein glycosylation in ageing-related diseases through study of Down syndrome as accelerated ageing condition
Description: Croatia (and the whole of Europe) are suffering from the most unfavourable demographic trends They include high population-ageing rates and an increasing incidence of age-related diseases. Recently, Prof. Lauc’s team discovered that immunoglobulin G (IgG) glycome pattern is an accurate biomarker of chronological and biological ageing, as well as systemic inflammation.Down’s Syndrome (DS) (trisomy 21 (T21)) causes extremely accelerated cellular and organism ageing and is therefore an excellent model of accelerated ageing. However, despite this, significant cohorts of people with DS are protected from ageing-related diseases, such as Alzheimer’s dementia (AD). Prof. Nižetić is an internationally leading researcher in DS and his team recently developed a new isogenic induced pluripotent stem cell (iPSC) model of DS.Protein glycosylation has never been systematically studied in the context of Down Syndrome. In our preliminary data from plasma samples of 10 DS individuals, compared to age-matched euploids, we detected extreme values in several glycan forms of IgG, indicating that markers of extremely accelerated ageing can be detected by studying glycome perturbations in DS.Aims: i) determine glycosylation of immunoglobulin G (IgG) in Down Syndrome (DS) by analysing 300 individuals with DS from 3 European population. In addition, they will be analysed based on co-morbidities, in particular early or late/absent onset of AD; (ii) examine the effect of specific chromosome 21 gene products on the glycosylation profiles; (iii) establish the effects of T21 on glycan profiles by comparing isogenic iPSCs that differ only on the presence of T21; (iv) search for novel glycan biomarkers predictive of early AD by comparing same glycan profiles in iPSCs (and derived neurons) from DS subjects with early dementia (in their 30s) with DS subjects with no dementia at age >60.
Funder: Hrvatska Zaklada za Znanost
Amount: €292,000
Funding type: grant
Funder scheme: PZS
Start date: 2019-10-01
End date: 2023-05-31
Investigator: Gordan Lauc
Institution: GENOS Ltd
Funded outputs count: 4
Funder award ID: PZS-2019-02-4277
OpenAlex ID: G4496623327