Amyloid P protein

Neuritic or senile plaques are extracellular protein deposits of fibrils and amorphous aggregates of P-amyloid protein.11 This formed protein is central to the pathogenesis of AD. The P-amyloid protein is present in a non-toxic, soluble form in human brains. In AD, conformational changes occur that render it insoluble and cause it to deposit into amorphous diffuse plaques associated with dystrophic neuritis.14 Over time, these deposits become compacted into plaques and the P-amyloid protein becomes fibrillar and neurotoxic. Inflammation occurs secondary to clusters of astrocytes and microglia surrounding these plaques. 

Increased cholesterol concentrations have been associated with AD. The cholesterol increases P-amyloid protein synthesis which can lead to plaque formation.16 Also, the apo E4 allele is thought to be involved in cholesterol metabolism and is associated with higher cholesterol levels.16... 

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). 

P Amyloid protein aggregation, leading to formation of plaques / Hyperphosphorylation of tau protein, leading to intracellular NFT development and collapse of microtubules / Inflammatory processes—levels of multiple cytokines and chemokines are elevated in AD brains / Neurovasculature dysfunction / Oxidative stress / Mitochondrial dysfunction... 

Pathological conditions are also linked to posttranslational modifications such as oxidized histidine residues found in P-amyloid protein of Alzheimer s patients, or conformational variants in the case of prion-induced encephalopathies. The development of sensitive MS tools and proteomics techniques is playing an active role in the precise description of these mechanisms.97,98... 

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). 

P-Amyloid protein increases toxic effects of glutamate in neuron cell growth. 

L. Meda, M.A. Cassatella, G.I. Szendrel, L. Otvos, P. Baron, M. Villalba, D. Ferrari and F. Rossi, Activation of microglial cells by p-amyloid protein and interferon-y, Nature 374 (1995) 647-650. 

Accumulation of P-amyloid proteins in the brain is one of the hallmarks of Alzheimer s disease. Dietary curcumin at low dose (160ppm) and high dose (5000ppm) significantly lowered oxidized proteins and interleukin 1-P, a pro-inflammatory cytokine... 

Fig. 6 Complex mechanism-P amyloid-protein interaction. (From Ref. i l)...

Itoh, A., Nitta, A., Nadai, M., Nishimura, K., Hirose, M., Hasegawa, T. et al., 1996. Dysfunction of cholinergic and dopaminergic neuronal systems in p-amyloid protein-infused rats. J. Neurochem, 66. 1113-1117. 

The selective aerobic oxidation of primary alcohols to aldehydes, but not secondary alcohols to ketones, is reminiscient of the chemistry catalyzed by the Cu-dependent enzyme, galactose oxidase (39). Similarly, the Cu-binding P-amyloid protein relevant to Alzheimer s disease promotes aerobic oxidation of cholesterol, a primary alcohol (cholesterol oxidase activity) (40). The Cu-dependent amine oxidases catalyze the aerobic oxidation of amines to aldehydes (41), the hydration products of imines. Each of these enzymes that promotes aerobic oxidation of primary alcohols and amines to the same products as Ni(TRISOX) catalyze the net reaction in Equation 1. If the net reactions... 

William Klunk and Chester Mathis vadiolabelled a fluorescent dye, related to Congo Red, labeled with fluorine-18, that is bound by P-amyloid protein in plaques found in the brain of patients with AD. After years of research, they developed a dye with 34 times the affinity for amyloid than Congo Red. Some think that P-amyloid is the cause of AD, whereas others think it is the result Patients with Down syndrome carry an extra copy of the amyloid gene, and they develop brain plaques and symptoms of AD when they reach middle age. 

P-Amyloid protein in cerebrospinal fluid is also used as a biomarker for AD. Research in mouse models of the disease has shown that greater amounts of amyloid-containing plaques in the brain are associated with lower levels of a specific protein fragment, P-amyloid 42 (Ap42), in cerebrospinal fluid. 

Jarrett, J.T., Berger, E.P. and Lansbury, P.T., Jr. 1993. The carboxy terminus of the P amyloid protein is critical for the seeding of amyloid formation Implications for the pathogenesis of Alzheimer s disease. Biochemistry 32 4693-4697... 

Pike, C.J., Walencewicz, A.J., Glabe, C.G. and Cotman, C.W. 1991. In vitro aging of P-amyloid protein causes peptide aggregation and neurotoxicity. Brain Res. 563 311-314... 

Mandelli, G. R. Maiorana, S. Imbimbo, B. P. Borsato, G. VUlani, P. P Lamperti, M. G. Colibretti, M. L. Triarylmethylene derivatives interfere with the aggregation process of P-amyloid proteins. Ital. Appl. rr 2000MI0707, 2001 Chem. Abstr. 2002,137, 299900. 

An in vivo study on rats showed that daily oral administration of secur-inine at 20—40 mg/kg could reverse the impairment of spatial memory caused by a single dose of p-amyloid protein 25—35 (intracerebroventricular injection). 

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