Description (from grant):
We will use neuropathology, including post-mortem MRI, vascular pathology, image processing, and registration to analyze post-mortem brains related to Alzheimer’s disease (AD) and AD-related dementia (ADRD) through MRI-histopathology analysis. MRI and histopathology are two key methods for all research into age-related cognitive impairment and dementia and they have brought key insights into disease mechanisms and therapeutic implications. A major challenge is to characterize the integrative properties of these two modalities, which differ in resolution, coverage, and markers; furthermore, in vivo, vascular abnormalities by nature are difficult to be characterized on post-mortem exams. Post-mortem MRI has emerged as a technique to bridge the gap but necessary techniques are still not fully developed. We propose to develop novel post-mortem MR imaging protocols and computational tools to enable the collection of multi-modal multi-scale brain MR/histopathology/ proteomics data analysis to advance our understanding of gray and white matter neurodegeneration associated with vascular contributions to cognitive impairment and dementia (VCID). An important aim is to develop a multi-modality atlas and database of the human medial temporal lobe (MTL) and prefrontal cortex (PFC) pathology based on co-registered multimodal and multiscale MRI and neuropathology data from a well-characterized cohort at NYU Langone Health ADRC that includes AD, TBI-related and other ADRD vs control subjects, focusing on Aβ, Tau, vascular, and microstructural pathology. The multi-modality vascular and microstructural atlases will be reconstructed and integrated with vascular pathology staining.