Neurofibrillary tangles in Alzheimer

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). 

Siedlak, S.L., Cras, P., Kawai, M., Richey, P. and Perry, G. (1991) Basic fibroblast growth factor binding is a marker for extracellular neurofibrillary tangles in Alzheimer disease. J. Histochem. Cytochem. 39 899-904. 

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. 

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. 

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... 

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. 

Gotz J, Chen F, van Dorpe J, Nitsch RM (2001) Formation of neurofibrillary tangles in P3011 tau transgenic mice induced by Abeta 42 fibrils. Science 293 1491-1495 Gotz J, Ittner LM (2008) Animal models of Alzheimer s disease and frontotemporal dementia. Nat Rev Neurosci 9 532-544... 

Although the cause of Alzheimer s disease remains unknown, investigators have discovered Alzheimer s patients have abnormal clumps of amyloid plaques and tangled bundles of fibers called neurofibrillary tangles in parts of their brain. 

---