Dystrophic neurite

DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N. Aggregation of Huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 1997 277 1990-1993. 

Dystrophic neurites show decreased spine density and decreased spine stabilization with increasing proximity to the plaque core [20]. Ca2+-sensi-tive dyes reveal a profound elevation in Ca2+ in neurites that are closer to the plaque core [21]. The cause of this Ca2+ dysregulation is unknown, but it is interesting that host defense mechanisms associated with NPs,... 

Studies that have focused on neuritic response to the NP rather than to presence of the plaque core itself have been more successful in finding a relationship between plaque-associated dystrophic neurites and dementia [30]. These studies suggest that plaque cores per se may only be an initiating event and that the gradual effects of the plaque core on adjacent neuronal pathway architecture may actuate the ultimate disruption of function. The timeframe over which the latter occurs, and the nature of how plaque-induced changes in synaptic connectivity ultimately affect cognition, is not known. 

Blanchard V, Moussaoui S, Czech C, Touchet N, Bonici B, Blanche M, Canton T, Jedidi 1, Gohin M, Wirths O, Bayer TA, Langui D, Duyckaerts C, Tremp G, Pradier L (2003) Time sequence of maturation of dystrophic neurites associated with Abeta deposits in APP/PS 1 transgenic mice. 

Praprotnik D, Smith MA, Richey PL, Vinters H V, Perry G (1996) Filament heterogeneity within the dystrophic neurites of senile plaques suggests blockage of fast axonal transport in Alzheimer s disease. Acta Neuropathol (Berl) 91 226-235... 

Besides the neuritic plaque, the other diagnostic lesion of AD is the neurofibrillary tangle. Tangles are non-membrane-bound masses of paired helical filaments, usually intermixed with straight filaments, found in the perinuclear cytoplasm of many limbic and cortical neuronal cell bodies. Smaller bundles of these abnormal filaments may occur in many, but not all, of the cortical dystrophic neurites found within and also separate from the neuritic plaques. Tangles are also observed in neurons of the subcortical nuclei (e.g., the cholinergic septal nuclei and nucleus basalis of Meynert) that project widely to limbic and association cortices rich in A/9 deposits. 

The transformation of immature, diffuse SPs composed almost exclusively from amyloi-dogenic Aj342 into the mature, neuritic SPs is poorly understood. It appears to be a continuous process, with numerous intermediates observable in the postmortem brains. The construction and composition of mature, neuritic SPs are fairly complex processes, in which the core consists mainly of A)340/42 and Aj3x-40/42 fragments and is surrounded by dystrophic neurites, activated microglia, and reactive astrocytes (96). In neuronal cultures conditioned by Aj8-treated astrocytes, but not di-... 

The dentate gyrus is a major site of neuropathology in FTLD-TDP (frontotemporal lobar degeneration with transactive response DNA-binding protein of 43 kDa proteinopathy). Most laminae of the cerebral cortex are affected. CRN mutation cases are quantitatively different from sporadic cases while cases with associated hippocampal sclerosis and AD have increased densities of dystrophic neurites and abnormally enlarged neurons, respectively. There is little correlation between the subjective assessment of subtypes and the more objective quantitative data [98]. Atrophy of the corpus callosum in AD is independent of white matter lesions and may be associated with cognitive deterioration [99],... 

The senile plaques represent extracellular round or ovoid structures, their diameters ranging between 1.5 and 20 nm. Typically, these plaques consist of three components abnormal nerve processes, glial processes and a central or amyloid core. There are different stages in plaque development primitive plaques consisting of neuritic components only, the classic plaque with central amyloid core surrounded by dystrophic neurites and, in the final stage, the bumed-out plaque with... 

AD is characterized by plaques surrounded by dystrophic neurites, NFTs, and regional atrophy caused by neuronal loss. The pattern of damage is not distributed uniformly through the brain. Cell loss is particularly severe in pyramidal nenrons in layers 111 and IV of the neocortex, as well as in glutamate-innervated cortical and hippocampal neurons (Albin and Greenamyre, 1992). The destruction of this neuronal population correlates with clinical severity ante mortem more than 90% are lost by end-stage (Bussiere et al., 2003). 

There are two major forms of plaques neuritic and diffuse. Neuritic plaques are composed of extracellular deposits of Ap surrounded by dystrophic neurites. Diffuse plaques are amorphous extracellular deposits of AP-immunoreactive granular material that lack neurites, and are thought to precede neuritic plaques. 

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. 

We performed a systematic analysis of the brain neuropathologic changes in eight patients with VCP mutations and identified ubiquitin-positive neuronal intranuclear inclusions and dystrophic neurites [28] (see Plate 15.12), making VCP disease another example of familial frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Neumann et al. [29] found that a hyperphosphory-... 

Alterations in UPS fnnction have been implicated in the pathogenesis of a variety of sporadic and familial neurodegenerative diseases including Parkinson disease, Alzheimer disease, polyglutamine repeat diseases, and ALS [63-65]. Mizuno et al. [66] called VCP "vacuole-creating protein" and demonstrated that VCP was observed in ubiquitin-positive intraneuronal inclusions in both motor neuron disease with dementia, and ballooned neurons in Creutzfeldt-Jakob disease. In Alzheimer disease, VCP has been found in dystrophic neurites while... 

In AD there are a number of associated abnormalities on the cellular and subcellular level that include dystrophic neurites, the activation of genes from the signaling pathways or the deficiency of the mitochondrial function. Diet supplementation with MCT oil favors the increase of the circulating ketone bodies, which are a good secondary energy sources for the... 

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