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 accum ulation of amyloid beta-protein (A beta) precedes neurofibrillary tangle fo rmation or neuronal loss in the cortex. Although this temporal profile has been proved in the neocortex by silver staining and immunocytochemical meth ods, CA1 of the hippocampus exhibits a distinct temporal profile during nor mal aging: the formation of neurofibrillary tangles precedes senile plaque formation. This temporal profile has been further confirmed by two-site enz yme immunoassay (EIA) quantitation of sodium dodecyl sulfate (SDS)-dissocia ble A beta 42; neurofibrillary tangles are already present despite undetect able levels of SDS-dissociable A beta 42, However, when the same specimens were subjected to Western blotting, many cases with or without neurofibrill ary tangles showed some accumulation of SDS-stable A beta dimers that canno t be detected by EIA, Thus, the temporal profile prerequisite for the hypot hesis is still valid in CA1, and this finding also suggests that SDS-stable A beta dimers have some significant effects on CAT pyramidal neurons, whic h are most vulnerable to neurofibrillary tangle formation.