Apolipoprotein E immunoreactivity within neurofibrillary tangles: relationship to Tau and PHF in Alzheimer's disease

The present immunohistochemical study determined the relationship between ApoE and the expression of the cytoskeletal protein tau (Tau2) and paired helical filaments (PHF), within the magnocellular neurons of the nucleus basalis of Meynert and layer II stellate neurons of the entorhinal cortex in Alzheimer's disease (AD). Although nearly all ApoE immunoreactive perikarya within these two brain regions were PHF immunoreactive, not all PHF and Tau2 containing neurons stained for ApoE in AD. Moreover, more Tau2-immunostained neurons, as compared to PHF, were ApoE immunonegative. This was particularly evident in a population of control subjects which exhibited AD-like pathology intermediate between the AD and normal aged individuals. Thus, neurons within the nucleus basalis of Meynert and entorhinal cortex layer II stellate exhibit evidence of cytoskeletal pathology prior to displaying ApoE. These observations suggest that (1) ApoE plays a secondary role in NFT formation or (2) this protein is accumulated within these neurons in response to reparative process(es) induced by NFT-associated neuronal damage.