| http://purl.uniprot.org/citations/11063718 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/11063718 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/11063718 | http://www.w3.org/2000/01/rdf-schema#comment | "Amyloidogenic processing of the amyloid precursor protein (APP) with deposition in brain of the 42 amino acid long amyloid beta-peptide (A beta(42)) is considered central to Alzheimer's disease (AD) pathology. However, it is generally believed that nonfibrillar pre-amyloid A beta(42) deposits have to mature in the presence of A beta(40) into fibrillar amyloid plaques to cause neurodegeneration. Here, we describe an aggressive form of AD caused by a novel missense mutation in APP (T714I) directly involving gamma-secretase cleavages of APP. The mutation had the most drastic effect on A beta(42)/A beta(40) ratio in vitro of approximately 11-fold, simultaneously increasing A beta(42) and decreasing A beta(40) secretion, as measured by matrix-assisted laser disorption ionization time-of-flight mass spectrometry. This coincided in brain with deposition of abundant and predominant nonfibrillar pre-amyloid plaques composed primarily of N-truncated A beta(42) in complete absence of A beta(40). These data indicate that N-truncated A beta(42) as diffuse nonfibrillar plaques has an essential but undermined role in AD pathology. Importantly, inhibiting secretion of full-length A beta(42 )by therapeutic targeting of APP processing should not result in secretion of an equally toxic N-truncated A beta(42)."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/9.18.2589"xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/9.18.2589"xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Wang R."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Wang R."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Kroisel P.M."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Kroisel P.M."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Backhovens H."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Backhovens H."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Cruts M."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Cruts M."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "De Jonghe C."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "De Jonghe C."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "De Strooper B."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "De Strooper B."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Kleinert R."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Kleinert R."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Kumar-Singh S."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Kumar-Singh S."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Loefgren A."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Loefgren A."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Mercken M."xsd:string |
| http://purl.uniprot.org/citations/11063718 | http://purl.uniprot.org/core/author | "Mercken M."xsd:string |