Quantification of Alzheimer disease neuropathology using tissue microarrays

Alzheimer's disease (AD) is characterized by the hallmark pathologies of β-amyloid plaques and neurofibrillary tangles (NFTs), which vary across brain regions and between affected individuals. As a rapid research method to quantify hallmark pathologies and their relationships with the surrounding cytoarchitecture across the brain, we trialed tissue microarrays (TMAs) in combination with multiplex immunofluorescence and semi-automated image analysis. We assayed the hallmark pathologies across grey and white matter sites of 11 different brain regions and quantified astrocytes, microglia, and neurons in four AD cases and four age- and gender-matched controls. The results demonstrated that 2 mm cores differentiated AD-affected individuals from healthy donors. Regional amyloid loads corroborated the established spread from the neocortex to allocortex, pontine, and occasionally cerebellar regions. Similarly, NFT counts matched the pattern predicted by Braak staging. Contrasting with the two hallmark pathologies, regional cell numbers were similar between cases and controls although cell counts were affected by variable staining quality. These results suggest that TMAs in combination with multiplex immunofluorescence and image analysis offer a powerful research tool for the rapid assessment of brain-wide AD neuropathological change in postmortem tissue. This quick assessment allows an informed selection of regions for more comprehensive investigations.