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Brain Pathol. 2012 Jul;22(4):472-84. doi: 10.1111/j.1750-3639.2011.00542.x. Epub 2011 Nov 14.

Novel antibody capture assay for paraffin-embedded tissue detects wide-ranging amyloid beta and paired helical filament-tau accumulation in cognitively normal older adults.

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Department of Pathology, University of Washington, Seattle, USA.


Quantifying antigens in formalin-fixed tissue is challenging and limits investigation in population-based studies of brain aging. To address this major limitation, we have developed a new technique that we call "Histelide": immunohistochemistry (HIST-) and enzyme-linked immunosorbent assay (ELISA) (-EL-) performed on a glass slide (-IDE). We validated Histelide in sections of prefrontal cortex from 20 selected cases: 12 subjects with clinically and neuropathologically diagnosed Alzheimer's disease (AD), either autosomal dominant or late-onset forms, and 8 clinical and neuropathologic controls. AD cases had significantly increased amyloid beta (Aβ) peptide and paired helical filament- (PHF-) tau per area of neocortex that was proteinase K-sensitive, and significantly decreased amount of synaptophysin. We next investigated prefrontal cortex from 81 consecutive cases of high-cognitive performers from the Adult Changes in Thought (ACT) study, a population-based study of brain aging and incident dementia. As expected, latent AD was common in this group; however, our results quantified widely individually varying levels of Aβ peptides and PHF-tau among these high-cognitive performers. This novel approach obtains quantitative data from population-based studies, and our initial studies with high-cognitive performers provide important quantitative insights into latent AD that should help guide expectations from neuroimaging and prevention studies.

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