Evidence that transmitter-containing dystrophic neurites precede those containing paired helical filaments within senile plaques in the entorhinal cortex of nondemented elderly and Alzheimer's disease patients

摘要: Abstract Within the amygdala of elderly subjects and patients with Alzheimer's disease (AD), we recently found evidence suggesting amyloid β-protein (AβP) deposition occurs before appearance dystrophic neurites. Moreover, these data suggested neurites initially lack cytoskeletal pathology although time further maturation, display an altered cytoskeleton as evidenced by their immunoreactivity to Alz-50 paired-helical filaments (PHF). These findings are particular relevance our understanding sequence pathologic events in AD thus it has become important determine whether unique or representative a more general pattern which can be throughout brain. Using battery antibodies markers that characteristic (i.e., AβP, PHF, Alz-50), three peptidergic neurotransmitters (neurotensin, somatostatin, substance P), one neurotransmitter biosynthetic enzyme (choline acetyltransferase), examined entorhinal cortex (EC) groups (AD, normal elderly, group nondemented numerous senile plaques.) The EC was studied, part, because is well recognized brain region displaying severe and, most importantly, early changes. Like amygdala, immunoreactive (AβP-IR) thioflavine-S-positive plaques occur within Ec prior transmitter-, Alz-50, PHF-immunoreactive We also observed transmitter-immunoreactive absence PHF-immunolabeled transmitter- Alz-50-IR those containing PHF. Collectively, were similar seen reinforced concept AβP primary event plaque pathology, this subsequently followed retain transmitter phenotype yet cytoskeleton. With time, develop alterations