Alzheimer s disease amyloid precursor protein

Evin G, Zhu A, Holsinger RM, Masters CL, Li QX. Proteolytic processing of the Alzheimer s disease amyloid precursor protein in brain and platelets. J Neurosci Res 2003 74(3) 386—392. 

Wolf BA, Wertkin AM, Jolly YC, et al. Muscarinic regulation of Alzheimer s disease amyloid precursor protein secretion and amyloid p-protein production in human neuronal NT2N cells. J Biol Chem 1995 270 4916-4922. 

Weidemann, A., Paliga, K., Durrwang, U., Reinhard, F.M., Schuckert, O., Evin, G. and Masters, C.L. (1999) Proteolytic processing of the Alzheimer s Disease amyloid precursor protein within its cytoplasmic domain by caspase-like proteases, J. Biol. Chem. 274, 5823. 

Sauder JM, Arthur JW, Dunbrack RL Jr. 2000. Modeling of substrate specificity of the Alzheimer s disease amyloid precursor protein beta-secretase. J. Mol. Biol. 300 241 18... 

Narindrasorasak, S., Lowery, D.E., Altman, R.A., Gonzalez, D.P., Greenberg, B.D., and Kisilevsky, R. (1992). Characterization of high affinity binding between laminin and Alzheimer s disease amyloid precursor proteins. Lab. Invest. 67, 643-652. 

Fombonne J, Rabizadeh S, Banwait S, Mehlen P, Bredesen DE (2009) Selective vulnerability in Alzheimer s disease amyloid precursor protein and p75(NTR) interaction. Ann Neurol 65 294-303... 

Kang, J., Lemaire, H. G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K. H., Multhaup, G., Beyreuther, K., and Muller-Hill, B. (1987). The precursor of Alzheimer s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325, 733-736. 

The precursor of Alzheimer s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325, 733-736. 

Figure 11.1 The amyloid hypothesis in Alzheimer s disease. The transmembrane protein amyloid precursor protein (APP) is cleaved first by f> -secretase (BACE), then by y -secretase. The resulting peptidic fragment, AfSAO/42, is liberated, leading to plaque accumulation. These plaques are associated with neuronal degeneration.

Keywords Active vaccination Alzheimer s disease Amyloid Amyloid precursor protein Antibody titer Beta-pleated sheet Cerebral amyloid angiopathy Dementia Immunotherapy Monoclonal antibody Passive vaccination Senility... 

Citron M, Oltersodrf T, Haass C, Mc-Conlogue L, Hung AY, et al. 1992. Mutation of the /1-amyloid precursor protein in familial Alzheimer s disease increases /1-protein production. Nature 360 672-74... 

Iwai A, MasUah E, Yoshimoto M, et al. The precursor protein of non-Abeta component of Alzheimer s disease amyloid is a presynaptic protein of the central nervous system. Neuron. 1995 14(2) 467-475. 

Bellingham, S.A., et aL, Copper depletion down-regulates expression of Alzheimer s disease Amyloid-beta precursor protein gene. J Biol Chem, 2004. 

Amyloid precursor protein (APP) is the precursor of (3-amyloid, the main component of senile plaques found in the brain of Alzheimer patients. The production of (3-amyloid from APP to the cells from abnormal proteolytic cleavage of the amyloid precursor protein. Enzymes involved in this cleavage may be suitable targets for the therapy of Alzheimer s disease. 

This type of disease occurs in families and begins unusually at early age (i.e., onset below the age of 60). Approximately 10% of Alzheimer s disease are familial and are inherited in an autosomal dominant manner with high penetrance. Deterministic genes directly cause the disease. Mutations in three different genes encoding for the amyloid precursor protein (APP) and the presenilins 1 and 2 (PS1 and PS2) have been identified to be responsible for early-onset familial Alzheimer s disease. 

Alzheimer s disease in which the pathogenicity of amyloid peptides depends on proteases, namely secretases, involved in amyloid precursor protein (APP) maturation. This chapter will describe how the proteolysis of chemokines might participate in the neuropathogenesis of HIV infection, thus contributing to the development of the central nervous system disorder termed HIV-associated dementia (HAD). 

Zhao M, Su J, Head E, Cotman CW (2003) Accumulation of caspase cleaved amyloid precursor protein represents an early neurodegenerative event in aging and in Alzheimer s disease. Neurobiol Dis 14 391-403... 

Figure 18.2 Production of senile plaque (S/A4 amyloid protein. Amyloid fS4 protein (/S/A4) is part of a 695, 751 or 770 amino-acid amyloid precursor protein APP. This is a transmembrane protein which is normally cleared within the fi/A4 amino acid sequence to give short 40 amino-acid soluble derivatives. It seems that under some circumstances as in Alzheimer s disease, APP is cleared either side of the fi/A4 sequence to release the 42/43 amino acid P/A4 which aggregates into the amyloid fibrils of a senile plaque (a). (See also Fig. 18.5.) Some factors, e.g. gene mutation, must stimulate this abnormal clearage leading to the deposition of P/A4 amyloid protein as plaques and tangles and the death of neurons (b)...

Checler, F (1995) Processing of the /i-amyloid precursor protein and its regulation in Alzheimer s disease. J. Neurochem. 65 1431-1444. 

Wagner SL, Munoz B. Modulation of amyloid B-protein precursor processing as a means of retarding progression of Alzheimer s disease. J Clin Invest 1999 104 1329-1332. 

A universal postmortem hallmark of Alzheimer s disease (AD) is the presence of amyloid plaques in the brain. These plaques are mainly composed of a 39 to 42 amino acid peptide, referred to as A0 peptide, that is excised from a precursor protein, amyloid precursor protein (APP), by the sequential action of two proteases (Olsen et al., 2001). The first of the two cleavages of APP occurs at a site within the APP protein that is termed the P-site, and BACE has been clearly determined to be the enzyme responsible for this cleavage event. A small portion of the AD patient... 

Selkoe, D. J. (1998). The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer s disease. Trends Cell Biol. 8, 447-453. 

Figure 13.6. From left to right location of the P-amyloid region of amyloid precursor protein (APP) in relation to the neuronal membrane normal processing of APP inactivates P-amyloid abnormal processing of APP in Alzheimer s disease liberates intact P-amyloid.

Amyloid protein A 42-amino acid protein found in the core of the microscopic senile plaques in the brains of individuals with Alzheimer s disease, p-amyloid protein is synthesised from the much larger amyloid precursor protein (APP). 

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