Project overview
Bone Pathology and Biomarkers in Alzheimer’s Disease and Related Dementias (ADRD)
The second line of inquiry involves the connection between bone and neurological outcomes in Alzheimer’s Disease and related dementias (ADRD). I became involved in this project through a collaboration with Clifford Rosen regarding his research on the gene alpha synuclein and its role in bone and metabolic effects of ADRD. To help Dr. Rosen discover the translational significance of his mouse findings, I performed an analysis of FHS data to study bone loss and its relationship to dementia diagnosis and the associated molecular determinants. First we performed a rigorous study of either baseline bone density or prior bone loss as a predictor of incident dementia, correcting for confounders (in preparation). We are also discovering genomic and transcriptomic variables that contribute to this association. We have found the alpha synculein transcript expression in three tissues, bone, blood, and brain, shows lower expression with lower bone density and increased dementia severity and pathology, and is co-expressed with genes important in mitochondrial function and mitophagy. We hypothesize that pathological expression of alpha syncuclein in bone and brain tissues cause pathology through disruption of normal mitochondrial function. Applications of this work include more in depth understanding of ADRD pathology in central and peripheral tissues, and development of new biomarkers for ADRD prediction or therapeutic targets. While our manuscripts in this new research area are currently in preparation, I have published an invited editorial entitled, “Osteoporosis and Dementia: Establishing a Link” for the Journal of Bone Mineral Density Research with my colleagues Douglas Kiel and Cliff Rosen.
