Multiple molecular alterations and pathway dysregulations contribute to neurodegenerative diseases, in particular Alzheimer’s disease (AD), and to neuropsychiatric symptoms (NPS), and delirium. Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain largely unknown. To understand these, we investigate a cohort of longitudinally followed-up elder subjects with or without cognitive impairment, with comprehensive clinical, neuropsychological, brain imaging, and blood, and cerebrospinal fluid (CSF) biomarker characterization unique in Switzerland.

Data from this cohort, including multiple omics datasets covering different biological levels is investigated using state of the art statistical and machine learning approaches to identify and explore alterations related to cognitive impairment and NPS severity, and the clinical disease progression over time. Multi-omics integration reveals interrelations of the involved pathophysiological processes and allows a deeper exploration of biological pathway alterations at both the central nervous system and the systemic levels.

In vivo detection of the pathophysiological processes of AD is key to precise diagnosis and appropriate care. Established PET and CSF biomarkers accurately detect cerebral AD pathology but are of limited use in clinical practice due to their costs, invasiveness, or non-availability of the tools needed. Blood-based biomarkers provide an attractive alternative, allowing to identify patients that may benefit from further, more invasive and/or costly diagnosis, or for recruitment of participants in clinical trials. The groups’ ongoing efforts focus on the development of personalized diagnosis and prognosis models based on clinical, imaging and blood-based biomarkers, and their validation for clinical practice.

• Integrative multi-omics to investigate cerebral and systemic biological pathway alterations with clinical relevance in early Alzheimer’s disease (Swiss National Science Foundation : 320030_204886) – in collaboration with the University of Lausanne and University of Bern
• Molecular pathway alterations of neuropsychiatric symptoms in older people: integrative multi-omics based characterization and biomarker discovery
• Discovering complex connections between brain energy metabolism and Alzheimer disease: Metabolomics-led system’s wide clinical and experimental study (Synapsis Foundation – Alzheimer Research Switzerland - 2017-PI01)
• Clinical, psychosocial and biological determinants of subjective cognitive decline