Sophia Weiss

Sophia Weiss

Researcher | Docent
Telephone: +46852483507
Mobile phone: +46730462626
Visiting address: BioClinicum, Akademiska Stråket 1, J9:20, 17164 Stockholm
Postal address: H1 Neurobiologi, vårdvetenskap och samhälle, H1 Neurogeriatrik Schedin Weiss, 171 77 Stockholm
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About me

  • I am docent in medical biochemistry and neurobiology and research group leader for projects focusing on elucidating the roles of glycans in neurodegeneration. I obtained my PhD in biochemistry on mechanisms involved in the neurological disorder Niemann-Pick type C disease at Stockholm University in 1998. I received a postdoctoral fellowship at the Swedish University for Agricultural Sciences, 1999-2002, where I studied protein-glycan and protein-protein interactions involved in the regulation of serine proteases. I was subsequently awarded a fellowship as Assistant Professor at Uppsala University, where I studied the role of protein glycosylation for proteins involved in blood coagulation. I moved to Karolinska Institutet in 2010, where my research goal is to elucidate early pathophysiological alterations on Alzheimer disease and other neurodegenerative disorders. This research is crucial for finding novel early biomarkers and understanding early disease mechanisms. My main research topics are to identify and validate glycan biomarkers, study subcellular mechanisms in neurodegenerative diseases and elucidate the link between protein glycosylation and pathophysiological mechanisms in Alzheimer disease to guide to novel treatment strategies.   

Research

  • I am highly interested in elucidating the molecular mechanisms behind and finding novel early biomarkers for Alzheimer disease (AD) and other neurodegenerative diseases. I have studied molecular interactions important for the regulation of gamma-secretase, the last one of two enzymes that processes the amyloid precursor protein (APP) to generate the amyloid β-peptide (Aβ), which is known as a toxic agent in AD, and the component of amyloid plaques in the brains of AD patients. One of my main interests is to study the subcellular localization of the Aβ processing machinery in neurons. To this end I have set up super-resolution microscopy techniques to resolve fine subcellular details. By using these techniques, we have determined the synaptic localization of gamma-secretase, APP and Aβ in neurons at the nano-scale level. I also have a great interest in studying how alterations in protein glycosylation are related to the development of neurodegenerative diseases. We have shown that protein glycosylation is altered in brain, cerebrospinal fluid and blood in AD and that these alterations can predict future cognitive decline. These studies are important for developing new diagnostic assays and treatment strategies.

Articles

All other publications

Grants

  • Swedish Research Council
    1 January 2026 - 31 December 2029
    Our recent studies show that altered N-glycosylation of proteins in cerebrospinal fluid (CSF) and blood in nondemented individuals can predict future cognitive decline and Alzheimer´s disease (AD) dementia. We propose to elucidate the link between N-glycosylation and cognitive decline in this 5-year project. The overarching aim is to develop glycan and glycopeptide biomarkers for early detection and subgrouping of individuals at risk of developing dementia and decipher how glycans are related to disease mechanisms. Mechanistic studies will be performed by altering glycosyltransferase activities in neurons and studying the effects on morphology, subcellular localization and levels of pathogenic proteins by cutting-edge super-resolution microscopy and protein analysis. Time-course glycosylation alterations will be studied in animal models. Glycoproteomics will be performed to identify glycopeptide alterations in brain, cerebrospinal fluid and blood from AD and other dementias. The utility of glycopeptides as predictive biomarkers for AD or other dementias will be assessed by statistical analysis of associations with other biomarkers and, especially, with cognitive data in longitudinal cohorts. Mass spectrometric methods and well-plate assays will be implemented clinically. The findings from this project could revolutionize diagnostics in primary and secondary care by providing glycoprotein biomarkers for predicting future cognitive decline earlier than current biomarkers.
  • VINNOVA
    1 October 2021 - 30 September 2026
    Purpose and goal: Alzheimer´s disease and other dementias are among the biggest societal challenges of the coming decades. The innovation milieu PREDEM aims to prevent dementia disorders by developing and introducing new methods for early detection and investigation, accurate diagnostics and individualized prevention and treatment. The vision for PREDEM is that all people who are at risk of developing dementia are offered the best available preventive measures and treatments based on their individual circumstances. Expected results and effects: New tools and work procedures can lead to earlier detection of incipient dementia, faster and safer diagnostics, as well as better accessibility and adaptation of investigation methods to different patient groups. More accurate forecasting models can facilitate that the right efforts for prevention and treatment are implemented at the right time, and that the resources of healthcare and society are thus used in the best possible way. In the longer term, these measures are expected to lead to fewer people developing dementia. Approach and implementation: In the innovation milieu, we introduce digital tools and working methods for early detection and investigation of cognitive impairment. Moreover, we develop, validate and introduce new classes of biomarkers for precision diagnostics. We develop prediction models and decision support for individualized prevention and treatment and develop methods for evaluating cost-effectiveness of new diagnostic and treatment strategies as well as new payment models to ensure fast and equal access to cost-effective treatment.

Employments

  • Researcher, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 2011-

Degrees and Education

  • Docent, Karolinska Institutet, 2024

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