There are many active research projects accessing and applying shared ADNI data. Use the search above to find specific research focuses on the active ADNI investigations. This information is requested annually as a requirement for data access.
| Principal Investigator | |
| Principal Investigator's Name: | Petroula Proitsi |
| Institution: | King's College London |
| Department: | Institute of Psychiatry, Psychology and Neuroscie |
| Country: | |
| Proposed Analysis: | Dementia is one of the biggest public health challenges of the 21st century, yet there are still no effective treatments at the disease modification level. Blood metabolites closely represent the physiological status of an organism, reflecting what has been encoded by the genome, and modified by systemic and environmental exposures. Since metabolites are easily accessible and potentially modifiable markers through diet and lifestyle, they can hold special value in dementia research. Indeed, a number of metabolomics studies including ours have published associations with late midlife cognition, incident dementia and AD[1-4]. However, the exact nature of their association with AD and the underlying biological mechanisms remain unclear. We would like to request individual level genotyped and imputed data from the ADNI cohort (ADNI1/2/3 and ADNIGO) in order to investigate the shared genetic component and ultimately the causal relationship between blood metabolites and AD phenotypes. The ADNI AD phenotypes we would like to examine are diagnosis (AD versus controls / MCI), cognitive decline and disease progression (cognition outcomes for all groups at baseline and subsequent timepoints) and biomarkers (imaging, amyloid and tau biomarkers). We would additionally like to request NMR Nightingale Metabolomics data generated by the ADMC. Polygenic scores (PRS) represent the genetic tendency of an individual for a disease or trait and are an indispensible tool in a variety of analyses. We would therefore like to systematically evaluate the shared genetic risk between blood metabolites and AD phenotypes using PRS, ir order to investigate in detail the lipid polygenic enrichment in AD. Results from these analyses will enhance our understanding of common sets of genetic variants that are associated both with metabolite traits and AD and highlight the underlying biological pathways. These analyses will inform approaches that address causality such as Mendelian Randomization. For our PRS, we will utilize publicly available summary GWA-metabolite data (base sample) performed on different platforms including NMR, Metabolon and in-house lipidomics data generated using the AddNeuroMed and Dementia Case Register cohorts. These will then be correlated with the requested outcomes from the ADNI study (target sample). Covariates such as age, sex, APOE genotypes, education, and any other lifestyle/health variables available (such as childhood cognition, bmi, information on lipid medication, smoking, exercise, drinking and diet as well for lipids such as TG, HDL-C, LDL-C and Total cholesterol) will help to examine the associations with polygenic enrichment under different models. Metabolomic data generated on ADNI will help us evaluate the strength of our PRS and will also allow for further targeted downstream analyses. |
| Additional Investigators |
