title: Consistent immunohistochemical detection of intracellular beta-amyloid42 in pyramidal neurons of Alzheimer's disease entorhinal cortex.
abstract: We compared the effects of three pretreatment immunohistochemical techniques (no pretreatment, pepsin predigestion and heat pretreatment (HEAT)) for detecting intracellular beta-amyloid42 (Abeta42) in pyramidal neurons of formalin-fixed Alzheimer's disease (AD) cortices (n = 25). Although all three protocols immunostained Abeta42 in amyloid plaques using four commercially-obtained Abeta42 specific antibodies, only the HEAT protocol consistently detected prominent intracellular Abeta42 in pyramidal neurons. This suggests that the Abeta42 present in amyloid plaques may be structurally distinct from that located within the neurons perhaps due to differential binding proteins coupling or a consequence of formalin fixation. Detection of an abundant intracellular Abeta42 in neurons may provide alternate explanations for the origin of dense-core amyloid plaques in AD cortices other than the conventional chronic extracellular Abeta42 deposition hypothesis.
authors.affiliation: Johnson and Johnson Pharmaceutical Research and Development, Spring House, PA 19477, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: D'Andrea
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nagele
authors.forename: Hoau-Yan
authors.initials: HY
authors.lastname: Wang
authors.forename: Daniel H S
authors.initials: DH
authors.lastname: Lee
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D018728:Entorhinal Cortex / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009474:Neurons / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis* / Q000276:immunology; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology*; D012016:Reference Values; D015203:Reproducibility of Results
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)