Our Research Focus
Our lab focuses on integrating observations from in-vivo imaging and molecular ‘omics’ in the study of Alzheimer’s Disease and other neurodegenerative diseases, with the goal of discovering new biomarkers and therapeutic targets, and improving methods to speed the drug discovery process.
Research Themes and Projects:
- Theme I: Multiomics investigation of age-related dementias - focus on disease mechanisms and prediction
- Project I: Establishing the Neurochemical Fingerprint of Aging and Age-related Dementias Using Multimodal Metabolomics
- Project II: Using Multiomics Approaches to Distinguish Dementia Subtypes
- Theme II: Novel blood-based biomarker development in age-related dementias
Theme I: Project I
Establishing the Neurochemical Fingerprint of Aging and Age-related Dementias Using Multimodal Metabolomics
Readouts of the brain’s metabolite composition can provide key insights into the neurochemical fingerprint of aging, and age-related dementias such as Alzheimer’s disease (Badhwar et al., Brain 2019; Cuperlovic-Culf & Badhwar, Expert Opin Drug Discov 2020). We are combining two complementary and powerful approaches to obtain such readouts: in vivo ultra high-field (7 Tesla) magnetic resonance spectroscopy (MRS), and mass spectrometry-based metabolomics of brain-secreted extracellular vesicles (EVs) in blood. This project will help elucidate the critical role of metabolic pathways in healthy aging and disease.
Theme I: Project II
Using Multiomics Approaches to Distinguish Dementia Subtypes
Multiomics biomarkers that combine information from systems to molecular biological scales can help identify dementia (e.g. Alzheimer’s disease, Vascular Cognitive Impairment and Dementia) subgroups with homogeneous pathophysiological signatures (Badhwar et al., Brain 2019). We are integrating observations from in-vivo imaging and molecular ‘omics’ to increase the separation between and better distinguish dementia subtypes. This work will improve diagnostic and prognostic power as well as help select patients for clinical trials who are more likely to respond to the therapeutics being tested.
Theme II: Project I
Evaluating novel blood-based biomarkers in Alzheimer’s disease
Alzheimer’s disease (AD) has a complex, multifactorial pathology. Gold-standard diagnostic workup for AD, in the living patient, relies on biomarker evidence of amyloid-beta and hyperphosphorylated-tau protein deposits in the brain, detected using cerebrospinal fluid analyses and/or positron emission tomography (PET). However, the invasiveness and high-cost associated with these tests limit their widespread implementation in primary care and clinical trials. There thus exists a critical need for blood-based biomarkers that could serve as minimally invasive, widely available, and less costly AD diagnostic tools. We are evaluating brain-derived extracellular vesicles in blood (Badhwar & Haqqani, Alzheimers Dement 2020) as an innovative blood-based diagnostic biomarker of AD.