66 research outputs found
Distinct glutaminyl cyclase expression in EdingerāWestphal nucleus, locus coeruleus and nucleus basalis Meynert contributes to pGlu-AĪ² pathology in Alzheimerās disease
Glutaminyl cyclase (QC) was discovered recently as the enzyme catalyzing the pyroglutamate (pGlu or pE) modification of N-terminally truncated Alzheimerās disease (AD) AĪ² peptides in vivo. This modification confers resistance to proteolysis, rapid aggregation and neurotoxicity and can be prevented by QC inhibitors in vitro and in vivo, as shown in transgenic animal models. However, in mouse brain QC is only expressed by a relatively low proportion of neurons in most neocortical and hippocampal subregions. Here, we demonstrate that QC is highly abundant in subcortical brain nuclei severely affected in AD. In particular, QC is expressed by virtually all urocortin-1-positive, but not by cholinergic neurons of the EdingerāWestphal nucleus, by noradrenergic locus coeruleus and by cholinergic nucleus basalis magnocellularis neurons in mouse brain. In human brain, QC is expressed by both, urocortin-1 and cholinergic EdingerāWestphal neurons and by locus coeruleus and nucleus basalis Meynert neurons. In brains from AD patients, these neuronal populations displayed intraneuronal pE-AĪ² immunoreactivity and morphological signs of degeneration as well as extracellular pE-AĪ² deposits. Adjacent AD brain structures lacking QC expression and brains from control subjects were devoid of such aggregates. This is the first demonstration of QC expression and pE-AĪ² formation in subcortical brain regions affected in AD. Our results may explain the high vulnerability of defined subcortical neuronal populations and their central target areas in AD as a consequence of QC expression and pE-AĪ² formation
Cells Proliferating in Vitro to Local Brain Injury Are Primarily of Hematic Origin and Differ from Those Associated with Anterograde Degeneration
Initial response of silver-impregnated ?resting microglia? to stab wounding in rabbit hippocampus
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