The use of formic acid to embellish amyloid plaque detection in Alzheimer's disease tissues misguides key observations.

We compared our heat pretreatment method to the widely used formic acid pretreatment technique to immunohistochemically detect amyloid in control and Alzheimer's disease brain tissues. Both methods detected amyloid in plaques, neurons, ependymal cells, circulating monocytes, vascular smooth muscle and endothelial cells. Although there were no observable differences in the intensity of the amyloid labeling in these cell types using both pretreatment methods, there were considerable differences in the intensity of amyloid immunolabeling in the plaques. The formic acid produced much more intense amyloid labeling in the plaques than the heat method. With the heat method, the intensity of the amyloid labeling in the plaques was similar to that detected in nearby neurons suggesting a neuronal origin of plaques. Conversely, the intensity of the amyloid in nearby neurons and plaques was drastically different using the formic acid suggesting unique origins of amyloid. The obvious benefits of formic acid for increasing the sensitivity of amyloid plaque immunolabeling may artifactually emphasize plaques over amyloid-containing cells during analyses.

Lipofuscin and Abeta42 exhibit distinct distribution patterns in normal and Alzheimer's disease brains.

Our recent study has provided evidence that Abeta42, a 42 amino acid fragment of the amyloid precursor protein, accumulates intracellularly in vulnerable neurons. This study appears to show that neurons lyse and form dense-core amyloid plaques in Alzheimer's disease (AD) entorhinal cortex. Previous studies have suggested that intracellular Abeta42 co-localizes with lipofuscin in neurons and those increased levels of lipofuscin and Abeta42 are associated with AD. Other studies have questioned this relationship and suggested that beta-amyloid and lipofuscin are not co-localized and that their levels are independent of one another in AD and age-matched control tissues. In an effort to resolve this controversy, we investigated the relative spatial relationship of intracellular Abeta42 and lipofuscin in AD brains tissue using a novel combined immunohistochemical:histochemical staining protocol. Our results show separate and distinct localization patterns of Abeta42 and lipofuscin in neurons and amyloid plaques.