Synapse loss

PSl forms a complex with p-catenin (CTNNBl), increasing P-catenin stability, and P-catenin levels are markedly reduced in the brains of AD patients with PSl mutations (157). One pathological characteristic of AD is extensive synapse loss. PSl is localized at the synapse, where it binds N-cadherin and modulates its adhesive activity. PSl is essential for efficient trafficking of N-cadherin from the ER to the plasma membrane. PW-mediated delivery of N-cadherin to the plasma membrane is important for N-cadherin to exert its physiological function, and it may control the state of cell-cell contact (158). 

The loss of synapses and the formation of plaques and tangles are important factors in the pathogenesis of AD. A clear correlation between the synapse loss and cognitive performance has been observed. Some authors such as R. D. Terry [1985) have proposed that the physical basis for cognitive alterations in AD is the synapse loss observed in the neocortex. 

If the functional deficit in AD is the result of neuronal and synapse loss, the ideal strategy would be to use techniques to reestablish neuronal and synaptic viability. In this sense, trophic factors are very promising. The positive results obtained in animal models of AD with brain tissue implantations with NGF and the memory enhancement and learning from laboratory animals treated with NGF have opened new windows to the possibility of the clinical use of NGF to treat AD. However, the potential benefits of the NGF may be counterbalanced by its capacity to increase the P-APP synthesis, consequently having an adverse effect in the progression of the illness. The increase of the APP synthesis may not necessarily affect all APP isoforms equally. The possibility of aberrant synapses and of alterations in the metabolism of the t- and P-amyloid protein exists [F. Hefti et al. 1995). 

Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., and Katzman, R. (1991). Physical basis of cognitive alterations in Alzheimer s disease synapse loss is the major correlate of cognitive impairment. Ann Neurol 30, 572-580. 

Abstract Alzheimer s disease (AD) is the most common cause of dementia in the elderly and is characterized by senile plaques, neurofibrillary tangles, synapse loss, and progressive neuronal deficits. There is an abundance of evidence suggesting that oxidative stress is involved in the pathogenesis of Alzheimer s disease. Several investigations have revealed the presence of oxidation products of proteins, lipids, and DNA in postmortem tissue from AD patients, indices that are indicative of increased oxidative stress. In the present review we discuss the role of protein oxidation in the brain of subjects with AD and MCI. 

Terry RD, et al. Physical basis of cognitive alterations in Alzheimer s disease synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 1991 30 572-80. 

Keywords Neuroinflammadon Innate and adaptive immunity Neurodegenation, Synapse loss... 

Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL (2007) Natural Oligomers of the Alzheimer Amyloid-13 Protein Induce Reversible Synapse Loss by Modulating an NMDA-Type Glutamate Receptor-Dependent Signaling Pathway. J Neurosci 27 2866-2875. 

Yoshiyama Y, Higuchi M, Zhang B et al (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53 337-351... 

S. T. DeKosky, S.W. SchefF, Synapse loss in frontal cortex biopsies in Alzheimer s disease correlation with cogni-... 

The final stage of AD, known as LAD, carries Braak scores of IV-VI and a substantial presence of oxidative stress markers (Castegna et al. 2002a,b, 2003 Reed et al. 2008 Butterfield et al. 2013 Sultana et al. 2013). Clinically, this results in severe disability due to dementia and a great deal of required care. Similar to EAD, this dementia can be attributed at least in part due to the significant synapse loss and enlarged synapses found in LAD (Scheff et al. 1990). 

Svennerhohn, L. and Gottfries, C.G. (1994) Membrane lipids, selectively diminished in Alzheimer brains, suggest synapse loss as a primary event in early-onset form (type I) and demyehnation in late-onset form (type II). J. Neurochem. 62, 1039-1047. 

FIGURE 47.5 Traumatic brain injury causes cell death, synapse loss, axon damage, and astrocyte reactivity. 

Koffie, R.M., Meyer-Luehmann, M., Hashimoto, T, et al., 2009. Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc. Natl. Acad. Sci. USA 106, 4012-1017. 

Dong H, Martin MV, Chambers S et al (2007) Spatial relationship between synapse loss and beta-amyloid deposition in Tg2576 mice. J Comp Neiuol 500 311-321... 

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