Neurofibrillary tangles , Alzheimer

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). 

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]. 

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. 

Alzheimer s disease is the most common form of age-related dementia and one of the most serious health problems in the industrialized world. AD is an insidious and progressive neurodegenerative disorder that accounts for the vast majority of dementia and is characterized by global cognitive decline and the accumulation of P-amyloid deposits and neurofibrillary tangles in the brain. Family history is the second greatest risk factor for... 

Neuroanatomical and neuropathological basis of Alzheimer s disease Histological features of Alzheimer s disease include neuritic plaques and neurofibrillary tangles (Boiler and Duyckaerts 1997). Neuritic plaques are composed of extracellular deposits of j8-amyloid protein and apolipoprotein E and are found primarily in neocortex. j8-amyloid is derived from an amyloid precursor protein, and is suspected to be a chief causal factor in Alzheimer s disease pathology (Samuel et al. 1997). Neurofibrillary tangles are clusters of protein fibers found in the cell body and composed of tau protein, which normally serves as a cytoskeletal element. Neurofibrillary tangles progress from entorhinal cortex to hippocampus, and then to neocortical areas. 

As illustrated in the diagram below, domain swapping can also result in indefinite polymerization to form linear supramolecular structures. These may correspond to present-day polymers of proteins such as microtubules, or they may represent abnormal structures, like the straight and paired-helical filaments in the neurofibrillary tangles observed in the brain tissue of those afflicted with Alzheimer s disease. 

Moreover, all cells are not equally targeted in Alzheimer s disease, a disease that has discernable effects on consciousness (Perry et al., 1999). Large pyramidal cells of the frontal and temporal cortex, as well as the large pyramidal cells in CAl of hippocampus and subiculum, are the most susceptible to develop neurofibrillary tangles, to become dysfunctional and ultimately to die (Mann, 1996). It is the accumulation of abnormally hyperphosphorylated tau that disrupts the microtubular system of pyramidal cells in cortex and hippocampus both in experimental animal models and in Alzheimer s disease brain (Gong et al., 2000). 

Shoghi-Jadid K, Small GW, Agdeppa ED, et al (2002) Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J... 

One theory of the pathogenesis of Alzheimer s disease proposes that increased production or decreased secretion of the Ap peptides leads to accumulation of these peptides. A second theory proposes that an abnormal x-protein causes the formation of intracellular neurofibrillary tangles. x-Proteins are important in the maintenance of cytoskeleton function and axonal transport of proteins. Another theory is that Ap accumulation is a precipitating factor that is followed by the development of the x-enriched tangles in the dying neurons. 

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