Pathologic lesions in neurodegenerative diseases.

This chapter will discuss two of the most widely used approaches to assessing brain structure: neuroimaging and neuropathology. Whereas neuropathologic approaches to studying the central nervous system have been utilized for many decades and have provided insights into morphologic correlates of dementia for over 100 years, accurate structural imaging techniques "blossomed" with the development and refinement of computerized tomographic scanning and magnetic resonance imaging (MRI), beginning in the late 1970s. As Alzheimer disease progresses over time, there is progressive atrophy of the hippocampus and neocortex--this can be quantified and regional accentuation of the atrophy can be evaluated using quantitative MRI scanning. Furthermore, ligands for amyloid proteins have recently been developed--these can be used in positron emission tomography studies to localize amyloid proteins, and (in theory) study the dynamics of their deposition (and clearance) within the brain over time. Neuropathologic studies of the brain, using highly specific antibodies, can demonstrate synapse loss and the deposition of proteins important in AD progression--specifically ABeta and phosphor-tau. Finally, neuropathologic assessment of (autopsy) brain specimens can provide important correlation with sophisticated neuroimaging techniques.