P-amyloid formation

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... 

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... 

Additional factors may influence fibril stability in vivo. The glycan molecules and amyloid P component found in amyloid deposits may stabilize amyloid fibrils (Pepys, 2006, and references therein). Also, monomer concentration is important to amyloid formation and stability in vivo several amyloidoses are associated with elevated levels of the fibril precursor protein, and deposits regress when the levels of the precursor protein are sufficiently reduced (Pepys, 2006, and references therein). 

Olofsson, A., Ippel, H. J., Baranov, V., Horstedt, P., Wijmenga, S., and Lundgren, E. (2001). Capture of a dimeric intermediate during transthyretin amyloid formation. / Biol. Chem. 276, 39592-39599. 

Smith, D. P., Jones, S., Serpell, L. C., Sunde, M., and Radford, S. E. (2003). A systematic investigation into the effect of protein destabilisation on beta 2-microglobulin amyloid formation./. Mol. Biol. 330, 943-954. 

Because conformational epitopes are not easily mimicked with linear peptides, which can elicit nonspecific antibodies, several alternative strategies such as synthetic cyclic peptides have been developed [see e.g., (18)]. A similar conformational restriction was seemingly achieved with a P-amyloid peptide that was anchored to the surface of liposomes via hydrophobic tails introduced at its both N- and C-termini. The reconstituted peptide proved highly immunogenic and elicited antibodies that could significantly prevent amyloid plaque formation in a model system (70). 

Jarrett, J.T., Berger, E.P. and Lansbury, Jr. P.T. (1993) The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation implications for the pathogenesis of Alzheimer s disease. Biochemistry 32,4693 1697. 

Bush Al, Multhaup G, Moir RD, Williamson TG, Small DH, Rumble B, Pollwein P, Beyreuther K, Masters CL (1993) A novel zinc(ll) binding site modulates the function of the beta A4 amyloid protein precursor of Alzheimer s disease. J Biol Chem 268 16109-16112 Bush Al, Pettingell WH, Multhaup G, d Paradis M, Vonsattel JP, Gusella JF, Beyreuther K, Masters CL, Tanzi RE (1994) Rapid induction of Alzheimer A beta amyloid formation by zinc. Science 265 1464-1467... 

Ginsenoside Rgl, one of the major active ingredients isolated from Panax Ginseng, has neuroprotective effects in animal models with memory impairment. Intracerebroventricular (i.c.v.) okadaic acid (OKA), a potent phosphatase inhibitor, induced memory impairment, decrease of phospho-tau and phospho-GSK3p, and formation of p-amyloid deposits in the brain of treated rats. All these changes were reversed by Rgl [272],... 

Hybrid molecules composed of an aromatic moiety and the oc-aminoisobutyric acid p-sheet breaker elements may act as inhibitors of amyloid fibril formation. The D-Trp-Aib was shown to be an effective inhibitor of the formation of p-amyloid fibrils and oligomers both in vitro and in vivo [380],... 

Frydman-Marom A, Shaltiel-Karyo R, Moshe S, Gazit E (2011) The generic amyloid formation inhibition effect of a designed small aromatic p-breaking peptide. Amyloid 18 119-127... 

Ono K, Takasaki JI, Takahashi R, Ikeda T, Yamada M (2013) Effects of antiparkinsonian agents on p-amyloid and a-synuclein oligomer formation in vitro. J Neurosci Res 91 1371-1381... 

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