Presence of sodium dodecyl sulfate-stable amyloid beta-protein dimers in the hippocampus CA1 not exhibiting neurofibrillary tangle formation.
The amyloid cascade hypothesis of Alzheimer's disease postulates that accumulation of amyloid beta-protein (Abeta) precedes neurofibrillary tangle formation or neuronal loss in the cortex. Although this temporal profile has been proved in the neocortex by silver staining and immunocytochemical methods, CA1 of the hippocampus exhibits a distinct temporal profile during normal aging: the formation of neurofibrillary tangles precedes senile plaque formation. This temporal profile has been further confirmed by two-site enzyme immunoassay (EIA) quantitation of sodium dodecyl sulfate (SDS)-dissociable Abeta42; neurofibrillary tangles are already present despite undetectable levels of SDS-dissociable Abeta42. However, when the same specimens were subjected to Western blotting, many cases with or without neurofibrillary tangles showed some accumulation of SDS-stable Abeta dimers that cannot be detected by EIA. Thus, the temporal profile prerequisite for the hypothesis is still valid in CA1, and this finding also suggests that SDS-stable Abeta dimers have some significant effects on CA1 pyramidal neurons, which are most vulnerable to neurofibrillary tangle formation.
Department of Neuropathology,* Faculty of Medicine, University of Tokyo, Japan.
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H
Funato
M
M
Enya
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M
Yoshimura
M
M
Morishima-Kawashima
Y
Y
Ihara
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D019281:Dimerization; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology*; D009778:Occipital Lobe / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology*; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012967:Sodium Dodecyl Sulfate