A unified 3D reconstruction of microscopy and MRI in a brain showing Alzheimer's disease-related neuropathology.

To bridge between detailed post-mortem neuropathological assessments and Magnetic Resonance Imaging (MRI), we have created and share a three-dimensional (3D) account of an entire human brain with an intermediate Alzheimer's disease neuropathologic change. We combined multimodal imaging, using cryosectioning, histology, immunocytochemistry, and quantitative ultra-high field 7 Tesla (T) magnetic resonance imaging (MRI) at submillimeter resolution. Amyloid-β and phosphorylated-tau immunoreactivity, cell soma, and nerve fibers were visualized, together with quantitative MR parameters. All data were coaligned with at 200 μm resolution and are openly shared. The use of whole-brain sections allows for a detailed assessment of neuropathological alterations, revealing clear differences between the left and right hemispheres in terms of pathological load of amyloid-β and phosphorylated-tau in a single brain showing Alzheimer's disease neuropathologic change. This resource opens the door for a combination of detailed correlations between neuroimaging and neuropathological microscopy observations, as well as for detailed MRI validation.