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Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein
Transgenic mice that express high levels of human mutant APP support a primary role for APP/Aβ in the genesis of AD and could provide a preclinical model for testing therapeutic drugs.
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
It is reported that immunization of the young animals essentially prevented the development of β-amyloid-plaque formation, neuritic dystrophy and astrogliosis, and treatment of the older animals markedly reduced the extent and progression of these AD-like neuropathologies.
Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease
Results indicate that antibodies can cross the blood–brain barrier to act directly in the central nervous system and should be considered as a therapeutic approach for the treatment of Alzheimer disease and other neurological disorders.
Phosphorylation of Ser-129 Is the Dominant Pathological Modification of α-Synuclein in Familial and Sporadic Lewy Body Disease*
An invariant pattern of specific phosphorylation, truncation, and ubiquitination is also present in the detergent-insoluble fraction of brain from patients with familial Parkinson's disease as well as multiple system atrophy, suggesting a common pathogenic pathway for both genetic and sporadic Lewy body diseases.
Purification and cloning of amyloid precursor protein β-secretase from human brain
A membrane-bound enzyme activity that cleaves full-length APP at the β-secretase cleavage site is described and found to be the predominant β-cleavage activity in human brain, and it is found that human brain β- secretase is a new membrane- bound aspartic proteinase.
Functional gamma‐secretase inhibitors reduce beta‐amyloid peptide levels in brain
These studies represent the first demonstration of a reduction of brain Aβin vivo and will enable a clinical examination of the Aβ hypothesis that Aβ peptide drives the neuropathology observed in Alzheimer's disease.
Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids
It is demonstrated that Aβ is produced and released both in vivo and in vitro, and new opportunities for developing diagnostic tests for Alzheimer's disease and therapeutic strategies aimed at reducing the cerebral deposition of Aβ are offered.
Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice
The data demonstrate that the preseniiin mutations cause a dominant gain of function and may induce AD by enhancing Aβ42 production, thus promoting cerebral β-amyloidosis.
Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics.
If one or more of these varied approaches is ultimately proven to slow or prevent dementia, Alzheimer's disease will become a salient example of the successful application of reductionist biology to the most complex of organs, the human cerebral cortex.
Amyloid beta-peptide is produced by cultured cells during normal metabolism.
The unexpected identification of the 4K (M(r) 4,000) A beta and a truncated form of A beta in media from cultures of primary cells and untransfected and beta-APP-transfected cell lines grown under normal conditions provides the basis for using simple cell culture systems to identify drugs that block the formation or release of ABeta.