The authors confirm that we have no disclosures or conflicts of interest for this submission.
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Novel Antibody Capture Assay for Paraffin-Embedded Tissue Detects Wide-Ranging Amyloid Beta and Paired Helical Filament–Tau Accumulation in Cognitively Normal Older Adults
Article first published online: 14 NOV 2011
DOI: 10.1111/j.1750-3639.2011.00542.x
© 2011 The Authors; Brain Pathology © 2011 International Society of Neuropathology
Additional Information
How to Cite
Postupna, N., Rose, S. E., Bird, T. D., Gonzalez-Cuyar, L. F., Sonnen, J. A., Larson, E. B., Keene, C. D. and Montine, T. J. (2012), Novel Antibody Capture Assay for Paraffin-Embedded Tissue Detects Wide-Ranging Amyloid Beta and Paired Helical Filament–Tau Accumulation in Cognitively Normal Older Adults. Brain Pathology, 22: 472–484. doi: 10.1111/j.1750-3639.2011.00542.x
Publication History
- Issue published online: 14 JUN 2012
- Article first published online: 14 NOV 2011
- Accepted manuscript online: 14 OCT 2011 07:37AM EST
- Received 2 August 2011 Accepted 27 September 2011Published Online Article Accepted14 October 2011
Keywords:
- aging;
- Alzheimer's disease;
- ELISA;
- immunohistochemistry
Abstract
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.