Pathologic issues and new methodologies in the evaluation of non-Alzheimer dementias

There are numerous approaches to studying, using sophisticated morpho-anatomic and biochemical techniques, brain tissues originating from patients with non-Alzheimer (AD) type dementias. Many of these have been developed, often perfected, on tissues from AD patients, but can easily be extrapolated to individuals with non-AD neurodegenerative conditions or vascular dementia. They include quantitative morphometric techniques (to evaluate neuronal/glial/synapse density and organization), immunohistochemistry (using both commercial and easily made 'custom' primary antibodies and incorporating confocal laser microscopy), and in situ hybridization (ISH). More recently, patterns of gene expression can be evaluated in individual cells or groups of cells using highly sensitive and specific microdissection in conjunction with appropriate molecular biologic techniques. Finally, high throughput analysis of patterns of gene expression can be evaluated using cDNA microarrays, while tissue microarrays (TMAs) allow efficient comparative study of localization of distinct gene products across 100s of tissue specimens arrayed in a single paraffin block. These techniques are certain to facilitate rapid advances in tissue-based investigation of non-AD dementias, and allow for the study of human neurodegenerative diseases at a level of sophistication that was once thought only feasible in animal tissues and experimental systems. (C) 2004 Elsevier B.V. All rights reserved.