QUANTIFICATION OF BETA-APP IMMUNOREACTIVE PRE-ALPHA CELLS IN THE ENTORHINAL CORTEX USING IMAGE-ANALYSIS

The neuropathological diagnosis of Alzheimer's disease requires an ass essment of the quantity of pathology present. Advances in molecular bi ology have highlighted the role of beta-amyloid precursor protein (bet a APP) in the pathogenesis of the disease. This protein is found in ne urons and other cells and many neuropathological studies would benefit from a method which generates reliable data on the numbers of cells c ontaining significant amounts of the protein. Classically, generation of such data would have involved laborious manual counting. This parti cular approach carries low levels of inter- and intra-rater reliabilit y and is much dependent on the skill and experience of the operator. W e have used immunocytochemistry to specifically define a single cell p opulation, pre-alpha cells, containing beta APP, and have developed a computerized cell counting programme that can reliably quantify these cells in human post-mortem brain samples. We have obtained a high leve l of accuracy (>95%) and efficiency in identifying and quantifying tar get cells and have demonstrated that our protocol can be used effectiv ely by both novice and expert. This method could be easily configured to provide quantitative data for a wide range of immunocytochemically defined cell populations. (C) 1995 Academic Press Limited