Neurofibrillary

Alzheimer s disease Amount of m-calpain in the cytosolic but not the membranous fractions and in the neurofibrillary tangles of brain from Alzheimer s patients is increased37,38... 

The MAPs vary in number and relative abundance in different cell types MAP2 is principally found in dendrites, whereas tau is restricted to axons. This selective distribution of MAP2 molecules is the result of subcellular sorting of its messenger RNA (Lewis et al., 1989). Currently, there is interest in the observation that tau is a component of the neurofibrillary tangles of Alzheimer s disease (Goedert et al., 1989). 

Goedert, M., Spillantini, M.G., Jakes, R., Rutherford, D., Crowther, R.A. (1989). Multiple isoforms of human microtubule-associated protein tau Sequences and localization in neurofibrillary tangles of Alzheimer s disease. Neuron 3, 519-526. 

Despite its characteristic symptoms and even after the exclusion of other established causes, AzD can only be reliably diagnosed by neuropathology and microscopic examination of the brain. Indeed that is how it came by its name. In 1907, a German physician, Alois Alzheimer, described two distinct post-mortem changes in the brain of a woman patient who had died with an unusual mental illness. These were the now characteristically accepted markers of the disease, namely senile plaques and neurofibrillary tangles (Fig. 18.1). 

In fact no consistent correlation has been found between the appearance, distribution and number of amyloid plaques and either neuronal loss or the degree of dementia, although the latter correlates with the number of neurofibrillary tangles, which tend to precede plaques in appearance by some years. Also cortical amyloid deposits can be found in non-demented elderly patients. Thus the basic question appears to be does the disease process, whatever that is, cause the development of AzD as well as the production of jS-amyloid or is there production of S-amyloid, which then causes AzD Consensus supports the latter but it is not proven. 

It has been estimated that up to 15% of head injuries may lead to AzD with dementia being common among boxers dementiapugilistica). Certainly such trauma is associated with diffuse amyloid deposits (not plaques) and a number of neurofibrillary tangles apparently identical to those in AzD. 

Arriagada, P.V., Louis, D.N., Hedlcy-Whyte, E.T. and Hyman, B.T. (1991). Neurofibrillary tangles and olfrictory dysgenesis. Lancet 337, 559. 

Namba, Y., Kawatsu, K., Izumi, S., Ueki, A. and Ikeda, K. (1992). Neurofibrillary tangles and senile plaques in brain of elderly leprosy patients. Lancet 340, 978. 

Pathologic hallmarks of the disease in the brain include neurofibrillary tangles and neuritic plaques (senile plaques)... 

The pathologic hallmarks of the disease in the brain include neurofibrillary tangles and neuritic plaques made up of various proteins, which result in a shortage of the neurotransmitter acetylcholine. These are primarily located in brain regions involved in learning, memory, and emotional behaviors such as the cerebral cortex, hippocampus, basal forebrain, and amygdala.11... 

Neurofibrillary tangles are intracellular and consist of abnormally phosphorylated tau protein which is involved in microtubule assembly. Tangles interfere with neuronal function... 

Neurofibrillary tangles Intracellular knots or clumps of neurofibrils seen in the cerebral cortex in Alzheimer s disease. 

Wakabayashi K, Hansen LA, Vincent I, Mallory M, Masliah E. Neurofibrillary tangles in the dentate granule cells of patients with Alzheimer s disease, Lewy body disease and progressive supranuclear palsy. Acta Neuropathol Berl 1997 93 7-12. 

The most definitive diagnosis of AD is a postmortem examination of the brain for the presence of two characteristic lesions the neuritic plaque (NP) and the neurofibrillary tangle. Both structures were originally described in 1906 by Alois Alzheimer using silver-based histological stains. The discovery of NPs was hailed as a watershed moment in the history of neurological disease as it helped shift society s perception of age-related dementia from social stigma to physical disease [2]. 

The availability of transgenic mice that faithfully recapitulate NP generation but fail to progress to neurofibrillary tangle formation, show little or no neuronal loss, and demonstrate modest at best cognitive deficits... 

Neurofibrillary tangle formation and dementia Figure 1 Hypothetical sequence of events in the NP-mediated progression of AD. 

Knowles, R. B., Chin, J., Ruff, C. T. and Hyman, B. T. (1999). Demonstration by fluorescence resonance energy transfer of a close association between activated MAP kinase and neurofibrillary tangles Implications for MAP kinase activation in Alzheimer disease. J. Neuropathol. Exp. Neurol. 58, 1090-8. 

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