Neurofibrillary tangles formation

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. 

Lue L. F., Brachova L., Civin W. H., and Rogers J. (1996). Inflammation, Abeta deposition, and neurofibrillary tangle formation as correlates of Alzheimer s disease neurodegeneration. J. Neu-ropathol. Exp. Neurol. 55 1083-1088. 

Candy JM, McArthur FK, Oakley AE, et al. 1992. Aluminum accumulation in relation to senile plaque and neurofibrillary tangle formation in the brains of patients with renal failure. J Neurol Sci 107 210-218. 

Figure 14.6. The role of apolipoprotein (Apo)E4 in the genesis of plaque and neurofibrillary tangle formation. Note that ApoE3 may have a protective effect against the activation of the microglia and the production of pro-inflammatory cytokines (such as interleukin-1).

Nagy Z, Esiri MM, Jobst KA, Johnston C, Litchfield S, Sim E, Smith AD (1995) Influence of the apoUpoprotein E genotype on amyloid deposition and neurofibrillary tangle formation in Alzheimer s disease. Neuroscience 69 757-761... 

Ramsden M, Kotilinek L, Forster C, Paulson J, McGowan E, SantaCruz K, Guimaraes A, Yue M, Lewis J, Carlson G, Hutton M, Ashe KH (2005) Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L). J Neurosci 25 10637-10647. 

Gotz, J., Chen, F., Van Dorpe, J. and Nitsch, R. M. Formation of neurofibrillary tangles in P3011 tau transgenic mice induced by AP fibrils. Science 293 1491-1495,2001. 

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. 

FIGURE 12-20. The amyloid cascade hypothesis of Alzheimer s disease (part 5). Formation of numerous neurofibrillary tangles also will eventually cause the neuron to cease to function and even to die. 

Figure 14.5. Diagrammatic representation of the role of tau protein (a) in the normal axon where it stabilizes the microtubules and (b) in the formation of neurofibrillary tangles (paired helical filaments) in the brain of patients with Alzheimer s disease.

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