AP-peptide

A better understanding of the biochemical nature of the amyloid core of the NP was only gained decades after its initial description. In 1984, it was discovered that boiling the plaque cores in formic acid could dissociate them, revealing that they were proteinaceous in nature and composed primarily of the Ap peptide [3]. 

Antibodies raised against the Ap peptide were subsequently used to identify more diffuse types of Ap-containing deposits in AD brain by immunohistochemistry. Diffuse Ap peptide deposits lack the... 

Recruited blood monocytes encountering local elevated levels of Ap peptide would then refold the Ap into a fibrillar conformation, thus forming the core of an NP adjacent to a blood vessel [24]. These plaque-bound monocytes differentiate into macrophages and mount an aberrant "wound response" through the release of neurotrophic and chemotactic agents, inducing an inappropriate ectopic sprouting response toward the... 

BACE2 cleavages, which occur in non-neural tissues, preclude the formation of Ap peptides and thus are thought to protect these organs from Ap amyloidosis [43],... 

Second, we described the successful outcomes of Ap immunotherapy in mutant mice with Ap amyloidosis. Unfortunately, in humans, although Phase 1 trials with Ap peptide and adjuvant vaccination were not associated with any adverse events, Phase 2 trials were suspended because of severe adverse reactions (meningoencephalitis) in a subset of patients [79,90]. The pathology in a single case, consistent with T-cell meningitis [90], was interpreted to show some clearance of Ap deposits, yet these regions... 

Cell culture studies have shown that carnosine is protective against the toxicity of the Ap-peptide which accumulates in the AD brain. The dipeptide prevented Ap-peptide (l-42)-induced glutamate release, but increased expression of the NMDA receptor. It was proposed that camosine s protective activity was exerted via regulation of glutamate release and independent of the carnosine-histidine-histamine axis (Fu et al,... 

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. 

For an octapeptide sequence taken from the C-terminal residues of the Alzheimer s Ap-peptide Lansbury et al. identified a large intensity enhancement for 13C-labeled modes that was sequence-dependent and assessed as largely due to interstrand dipole-coupling.1207,2351 Mendelsohn et al. found a similar effect by double labeling on alternate sites a peptide that formed a P-sheet-like structure in methanol.12501 Subsequent theoretical modeling showed this latter intensity enhancement to be a function of forming extended, flat, anti-parallel P-sheet structures,12511 and the overall effect to be highly position sensitive.12451... 

Table 6.2 Comparative Effects of Tea Extracts and Phenolic Compounds on Soluble and Insoluble Forms of Ap Peptides...

The value of the correlation coefficient for the data shown in Fig. 13.9 shows that the probability that neuronal dysfunction is not related directly to the aggregation of the Ap-peptide, in this system at least, is less than 1 in... 

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