Title: Novel antibody capture assay for paraffin-embedded tissue detects wide-ranging amyloid beta and paired helical filament-tau accumulation in cognitively normal older adults.
Authors: Postupna, Nadia; Rose, Shannon E; Bird, Thomas D; Gonzalez-Cuyar, Luis F; Sonnen, Joshua A; Larson, Eric B; Keene, C Dirk; Montine, Thomas J
Published In Brain Pathol, (2012 Jul)
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.
PubMed ID: 21999410
MeSH Terms: Aged; Aged, 80 and over; Aging; Alzheimer Disease/metabolism; Alzheimer Disease/pathology; Amyloid beta-Peptides/analysis*; Brain/metabolism; Brain/pathology; Enzyme-Linked Immunosorbent Assay/methods*; Female; Humans; Immunohistochemistry/methods*; Male; Middle Aged; Paraffin Embedding; tau Proteins/analysis*