Neurofibrillary tangles in Alzheimer’s disease

The microtubule-associated-protein tau is a component of the neurofibrillary tangles in Alzheimer s disease and a target of S100A1. PC 12 cells devoid of S100A1 were shown to be more resistant to A(3(25-35) peptide-mediated cell death and have lower levels of intracellular amyloid precursor protein (APP) (Zimmer et al., 2005). 

Makjanic J, McDonald B, Chen CPLH, et al. 1998. Absence of aluminum in neurofibrillary tangles in Alzheimer s disease. Neurosci Lett 240 123-125. 

Tau protein is a neuronal microtubule associated protein (MAP) that localizes primarily in the axon (Leger et al., 1994). It is one of the major and most-studied MAPs in the central nervous system (Alonso et al 2001). Tau has been recognized to play major roles in promoting microtubule assembly, stabilizing microtubules and maintaining the normal morphology of the neurons. Tau has been the focus of intense research for more than a decade after it was discovered to be a key component of neurofibrillary tangles in Alzheimer s disease (AD). 

Gamblin, T.C., Chen, F., Zambrano, A., et al. Caspase cleavage in tau Linking amyloid and neurofibrillary tangles in Alzheimer s disease. Proc. Natl. Acad. Sci. 100 (2003)... 

Kuusisto E, Salminen A, Alafuzoff I. (2002) Early accumulation of p62 in neurofibrillary tangles in Alzheimer s disease possible role in tangle formation. Neuropathol App Neurobiol 28, 228-237. 

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. 

Good PF, Perl DP, Bierer LM, et al. 1992b. Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer s disease A laser microprobe (LAMMA) study. Ann Neurol 31 286-292. 

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

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. 

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). 

FIGURE 12-15. Another key finding in Alzheimer s disease is the pathological finding of another degenerative structure called neurofibrillary tangles made up of abnormally phosphorylated tau proteins. 

Other areas of the human brain have not been studied in detail. In Alzheimer s disease, neurofibrillary tangles are found to colocalize with histamine in the tuberomammillary areas in the posterior hypothalamus1, and significantly reduced neuron numbers of the tuberomammillary nucleus in Alzheimer s brains33 have been reported. 

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