Neuropil threads

Protein aggregation is a common feature of all of the chronic human neurode-generative disorders. The intraneuronal inclusions in many of these diseases contain deposits of ubiquitylated proteins, indicating that perturbations of ubiquitin-dependent proteolysis may occur. The neuropathological hallmarks of AD are intraneuronal NFTs composed of hyperphosphorylated protein tau and extracellular amyloid plaques (12,23,24,191,207). Most of the ubiquitylated, hyperphosphorylated tau protein in NETs is monoubiquitylated, with the remainder polyubiquitylated, as the substrate of the 26S proteasome (258). The protein deposits in NET, neuritic plaques, and neuropil threads in the cerebral cortex of AD patients and those with... 

The IRP-1 is present at similar levels in both AD and control brains. In contrast, IRP-2 co-localizes with redox-active Fe in NFT, senile plaque neurites, and neuropil threads. Hence, alterations in IRP-2 might be directly linked to impaired iron homeostasis in AD [28]. 

Cullen KM. 1994. A novel nickel avidin-biotin-peroxidase method for histochemical visualization of neurofibrillary tangles, senile plaques, and neuropil threads. J Histochem... 

Guegan C, Vila M, Rosoklija G, Hays AP, Przedborski S (2001) Recruitment of the mitochondrial-dependent apoptotic pathway in amyotrophic lateral sclerosis. J Neurosci 21 6569-6576 Guo H, Albrecht S, Bourdeau M, Petzke T, Bergeron C, LeBlanc AC (2004) Active caspase-6 and caspase-6-cleaved tau in neuropil threads, neuritic plaques, and neurofibrillary teingles of Alzheimer s disease. Am J Pathol 165 523-531... 

In AD neurons, there are three main types of neurofibrillary lesions (NFLs) according to their intracellular localization neurofibrillary tangles (NFTs) inside the cell body and apical dendrites, and neuropil threads (NThs) in distal dendrites and dysrophic neurites, associated with senile plaques. Morphologically, three major subtypes of NFTs can be distinguished, corresponding to different evolutionary stages of these lesions. 

Braak H, Braak E, Strothjohann M (1994) Abnormally phosphorylated tau protein related to the formation of neurofibrillary tangles and neuropil threads in the cerebral cortex of sheep and goat. Neurosci Lett 171 1-4... 

CaM kinase II participates in the phosphorylation of tau (Baudier and Cole, 1987 Steiner et al., 1990). It phosphorylates a nnmber of other substrates in vitro, including MAP-2, tyrosine hydroxylase, synapsin 1, APP, and varions intermediate filament proteins such as vimentin, desmin, and GFAP (Colbran et al., 1989). In vitro, CaM kinase Il-phosphorylated tau inhibits microtnbnle assembly (Yamamoto et al., 1983 Yamamoto et al., 1985, 1988). It phosphorylates tau in vitro in such a way to slow its electrophoretic mobility (Baudier and Cole, 1987). Serine " (numbered according to the longest human tau isoform) is one of the major phosphorylation sites for CaM kinase II in vitro (Steiner et al., 1990). Immnnostaining of AD brain showed serine " phosphorylation only in neuronal soma, bnt not in neuropil threads and dystrophic neurites (Yamamoto et al., 2005). Tau phosphorylation in glia cells is unlikely due to CaM kinase II. 

Two types of protein deposits, the amyloid plaques and the neurofibrillary deposits (tangles, neuropil threads) characterize the pathology of Alzheimer s disease. The latter are composed of largely paired hehcal filaments, which are in turn made up mainly of an insoluble form of the microtubule-associated protein t (Brion et al. 1985). In the sequence of deposition of P-amyloid, Thal etal. (1999) found the first deposits in the temporal neocortex. The next regions affected were the hippocampal sector CAl and the entorhinal cortex. Thereafter, the molecular layer of the dentate gyrus and the parvopyramidal layer of the presubiculum became involved in P-amyloidosis. Finally, amyloid plaques occupied the dentate hilus and occasionally even the pre-a layer of the entorhinal cortex. 

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