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.
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.
authors: Department of Pathology, University of Washington, Seattle, USA.
authors: Nadia
authors: N
authors: Postupna
authors: Shannon E
authors: SE
authors: Rose
authors: Thomas D
authors: TD
authors: Bird
authors: Luis F
authors: LF
authors: Gonzalez-Cuyar
authors: Joshua A
authors: JA
authors: Sonnen
authors: Eric B
authors: EB
authors: Larson
authors: C Dirk
authors: CD
authors: Keene
authors: Thomas J
authors: TJ
authors: Montine
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D016875:tau Proteins / Q000032:analysis*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins