FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1544136870> ?p ?o ?g. }

• W1544136870 endingPage "739" @default.
• W1544136870 startingPage "738" @default.
• W1544136870 abstract "The goal of science, at its most fundamental level, is to construct hypotheses and thereafter to devise experiments that either disprove the hypothesis or, by not disproving it, provide additional support for the hypothesis. In the field of Alzheimer's disease (AD), the predominant hypothesis is the Amyloid Cascade Hypothesis, the original version of which posited that insoluble fibrillar amyloid β (Aβ) is central to disease pathogenesis.1Hardy JA Higgins GA Alzheimer's disease: the amyloid cascade hypothesis.Science. 1992; 256: 184-185Crossref PubMed Scopus (4969) Google Scholar In support of this hypothesis, Aβ fibrils have been found to be toxic in vitro,2Lorenzo A Yankner BA Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red.Proc Natl Acad Sci USA. 1994; 91: 12243-12247Crossref PubMed Scopus (1294) Google Scholar and, since then, considerable effort has been and continues to be made on developing therapeutic modalities that target Aβ fibrils. In this regard, transgenic mice that overexpress mutant forms of the Aβ protein precursor (AβPP) and develop extensive fibrillar Aβ-senile plaque deposits3Hsiao K Chapman P Nilsen S Eckman C Harigaya Y Younkin S Yang F Cole G Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice.Science. 1996; 274: 99-102Crossref PubMed Scopus (3671) Google Scholar have become invaluable, despite the fact that such mice do not provoke neurodegeneration or other features of AD, which would seem to disprove the hypothesis. That withstanding, such transgenic mice have become important screening tools for potential therapeutics, and of the many agents found to “treat” these mice (ie, reduce Aβ plaque deposits and rescue cognitive deficits), none has raised as much enthusiasm and expectations as the vaccination strategy.4Schenk D Barbour R Dunn W Gordon G Grajeda H Guido T Hu K Huang J Johnson-Wood K Khan K Kholodenko D Lee M Liao Z Lieberburg I Motter R Mutter L Soriano F Shopp G Vasquez N Vandevert C Walker S Wogulis M Yednock T Games D Seubert P Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse.Nature. 1999; 400: 173-177Crossref PubMed Scopus (2931) Google Scholar, 5Buttini M Masliah E Barbour R Grajeda H Motter R Johnson-Wood K Khan K Seubert P Freedman S Schenk D Games D Beta-amyloid immunotherapy prevents synaptic degeneration in a mouse model of Alzheimer's disease.J Neurosci. 2005; 25: 9096-9101Crossref PubMed Scopus (152) Google Scholar Around the same time that the vaccination approach was entering into human clinical trials, the original Amyloid Cascade Hypothesis1Hardy JA Higgins GA Alzheimer's disease: the amyloid cascade hypothesis.Science. 1992; 256: 184-185Crossref PubMed Scopus (4969) Google Scholar underwent a slight modification in which the emphasis switched to oligomeric, rather than fibrillar, forms of Aβ.6Hardy J Selkoe DJ The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics.Science. 2002; 297: 353-356Crossref PubMed Scopus (10863) Google Scholar Today, oligomeric Aβ is viewed, almost universally in the field, as the most toxic and, therefore, most important species.7Lesne S Koh MT Kotilinek L Kayed R Glabe CG Yang A Gallagher M Ashe KH A specific amyloid-beta protein assembly in the brain impairs memory.Nature. 2006; 440: 352-357Crossref PubMed Scopus (2415) Google Scholar What impact did this have for the clinical trial that targeted fibrillar amyloid? Before this question was answered, the clinical trial was suspended because of the development of encephalitis in a small percentage of individuals, an event that was subsequently blamed on the adjuvant.8Birmingham K Frantz S Set back to Alzheimer vaccine studies.Nat Med. 2002; 8: 199-200Crossref PubMed Scopus (84) Google Scholar However, two alternate explanations may be more relevant in explaining such an unexpected outcome. First, while initial studies in mice supported vaccination-mediated decreases in both fibrillar and oligomeric species,4Schenk D Barbour R Dunn W Gordon G Grajeda H Guido T Hu K Huang J Johnson-Wood K Khan K Kholodenko D Lee M Liao Z Lieberburg I Motter R Mutter L Soriano F Shopp G Vasquez N Vandevert C Walker S Wogulis M Yednock T Games D Seubert P Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse.Nature. 1999; 400: 173-177Crossref PubMed Scopus (2931) Google Scholar the paper in this issue of The American Journal of Pathology9Patton RL Kalback WM Esh CL Kokjohn TA Van Vickle GD Luehrs DC Kuo Y-M Lopez J Brune D Ferrer I Masliah E Newel AJ Beach TG Castano EM Roher AE Abeta peptide remnants in AN-1792-immunized Alzheimer's disease patients: a biochemical analysis.Am J Pathol. 2006; 169: 1048-1063Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar shows that oligomeric amyloid may, in fact, increase in human patients who received the vaccination (Figure 1). Specifically, while senile plaques were disaggregated in AD patients who received the vaccination, the amount of soluble amyloid was substantially increased when compared with nonvaccinated AD patients. Based on these findings, the authors suggest that the elevated pool of soluble amyloid may further impair neuronal function, reduce neural transmission, and promote neuroinflammation.9Patton RL Kalback WM Esh CL Kokjohn TA Van Vickle GD Luehrs DC Kuo Y-M Lopez J Brune D Ferrer I Masliah E Newel AJ Beach TG Castano EM Roher AE Abeta peptide remnants in AN-1792-immunized Alzheimer's disease patients: a biochemical analysis.Am J Pathol. 2006; 169: 1048-1063Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar In our opinion, such neuroinflammation may be a potential cause of the negative outcome of vaccination in some patients (ie, encephalitis). While the results of a related trial involving passive vaccination, to avoid adjuvant issues, are eagerly anticipated, the present findings essentially remove any “doubt” (sic) that amyloid is indeed responsible for AD. Simply, if patient health improves, it is because Aβ fibrils are removed. On the other hand, if patients fare worse, it is because of increases in oligomeric Aβ. Success or failure will equally support the Amyloid Hypothesis. However, as cited, in subgroup analysis, a percentage of patients may have benefited from the vaccination.10Hock C Konietzko U Streffer JR Tracy J Signorell A Muller-Tillmanns B Lemke U Henke K Moritz E Garcia E Wollmer MA Umbricht D de Quervain DJ Hofmann M Maddalena A Papassotiropoulos A Nitsch RM Antibodies against beta-amyloid slow cognitive decline in Alzheimer's disease.Neuron. 2003; 38: 547-554Abstract Full Text Full Text PDF PubMed Scopus (722) Google Scholar, 11Gilman S Koller M Black RS Jenkins L Griffith SG Fox NC Eisner L Kirby L Rovira MB Forette F Orgogozo JM Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial.Neurology. 2005; 64: 1553-1562Crossref PubMed Scopus (1123) Google Scholar Perhaps in such patients, clearance mechanisms enable rapid removal of Aβ oligomers, with the benefit lying in removal of fibrils. Thus, the question now becomes explaining this finding so future therapeutic efforts can be more successful. Such investigations are no doubt pending. Nonetheless, this vaccination strategy does result in an increase in soluble (oligomeric?) amyloid in some people, and this would be viewed as detrimental according to the current construct of the Amyloid Cascade Hypothesis. While the two mainline amyloid theories consider amyloid as toxic, a second alternate role for Aβ in AD must also be considered. We predicted originally that vaccination strategies were likely to fail,12Perry G Nunomura A Raina AK Smith MA Amyloid-beta junkies.Lancet. 2000; 355: 757Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar, 13Smith MA Atwood CS Joseph JA Perry G Predicting the failure of amyloid-beta vaccine.Lancet. 2002; 359: 1864-1865Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar not because of an increase in oligomeric amyloid, but because we suspect that Aβ is a protective consequence of the disease, not a cause of disease.14Lee HG Casadesus G Zhu X Takeda A Perry G Smith MA Challenging the amyloid cascade hypothesis: senile plaques and amyloid-beta as protective adaptations to Alzheimer disease.Ann NY Acad Sci. 2004; 1019: 1-4Crossref PubMed Scopus (140) Google Scholar, 15Rottkamp CA Atwood CS Joseph JA Nunomura A Perry G Smith MA The state versus amyloid-beta: the trial of the most wanted criminal in Alzheimer disease.Peptides. 2002; 23: 1333-1341Crossref PubMed Scopus (85) Google Scholar Our Alternate Amyloid Hypothesis16Lee HG Zhu X Nunomura A Perry G Smith MA Amyloid beta: the alternate hypothesis.Curr Alzheimer Res. 2006; 3: 75-80Crossref PubMed Scopus (96) Google Scholar posits that Aβ serves as a protective antioxidant and that its removal will exacerbate, rather than treat, disease. The paper by Roher and colleagues9Patton RL Kalback WM Esh CL Kokjohn TA Van Vickle GD Luehrs DC Kuo Y-M Lopez J Brune D Ferrer I Masliah E Newel AJ Beach TG Castano EM Roher AE Abeta peptide remnants in AN-1792-immunized Alzheimer's disease patients: a biochemical analysis.Am J Pathol. 2006; 169: 1048-1063Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar in this issue of the AJP gives us pause for thought on our original prediction12Perry G Nunomura A Raina AK Smith MA Amyloid-beta junkies.Lancet. 2000; 355: 757Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar, 13Smith MA Atwood CS Joseph JA Perry G Predicting the failure of amyloid-beta vaccine.Lancet. 2002; 359: 1864-1865Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar—perhaps, by increasing oligomeric Aβ, the vaccination strategy may work by increasing protective Aβ. In other words, for both the Amyloid Cascade Hypothesis and the Alternate Amyloid Cascade, the results of the immunization trial are the same: Heads we win, tails you lose! Amyloid-β Peptide Remnants in AN-1792-Immunized Alzheimer's Disease Patients: A Biochemical AnalysisThe American Journal of PathologyVol. 169Issue 3PreviewExperiments with amyloid-β (Aβ)-42-immunized transgenic mouse models of Alzheimer's disease have revealed amyloid plaque disruption and apparent cognitive function recovery. Neuropathological examination of patients vaccinated against purified Aβ-42 (AN-1792) has demonstrated that senile plaque disruption occurred in immunized humans as well. Here, we examined tissue histology and quantified and biochemically characterized the remnant amyloid peptides in the gray and white matter and leptomeningeal/cortical vessels of two AN-1792-vaccinated patients, one of whom developed meningoencephalitis. Full-Text PDF" @default.
• W1544136870 created "2016-06-24" @default.
• W1544136870 creator A5008252393 @default.
• W1544136870 creator A5021420538 @default.
• W1544136870 creator A5061884568 @default.
• W1544136870 creator A5071772212 @default.
• W1544136870 creator A5075477128 @default.
• W1544136870 date "2006-09-01" @default.
• W1544136870 modified "2023-10-01" @default.
• W1544136870 title "Amyloid-β Vaccination: Testing the Amyloid Hypothesis?" @default.
• W1544136870 cites W1546526125 @default.
• W1544136870 cites W1693283493 @default.
• W1544136870 cites W1981570625 @default.
• W1544136870 cites W1997035764 @default.
• W1544136870 cites W2001210466 @default.
• W1544136870 cites W2018695499 @default.
• W1544136870 cites W2038221712 @default.
• W1544136870 cites W2041883598 @default.
• W1544136870 cites W2075481535 @default.
• W1544136870 cites W2082429191 @default.
• W1544136870 cites W2096410114 @default.
• W1544136870 cites W2103440561 @default.
• W1544136870 cites W2112216133 @default.
• W1544136870 cites W2149086197 @default.
• W1544136870 cites W2150935454 @default.
• W1544136870 cites W2155347072 @default.
• W1544136870 cites W2157064933 @default.
• W1544136870 doi "https://doi.org/10.2353/ajpath.2006.060633" @default.
• W1544136870 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1698831" @default.
• W1544136870 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16936250" @default.
• W1544136870 hasPublicationYear "2006" @default.
• W1544136870 type Work @default.
• W1544136870 sameAs 1544136870 @default.
• W1544136870 citedByCount "17" @default.
• W1544136870 countsByYear W15441368702012 @default.
• W1544136870 countsByYear W15441368702017 @default.
• W1544136870 countsByYear W15441368702019 @default.
• W1544136870 countsByYear W15441368702020 @default.
• W1544136870 countsByYear W15441368702022 @default.
• W1544136870 crossrefType "journal-article" @default.
• W1544136870 hasAuthorship W1544136870A5008252393 @default.
• W1544136870 hasAuthorship W1544136870A5021420538 @default.
• W1544136870 hasAuthorship W1544136870A5061884568 @default.
• W1544136870 hasAuthorship W1544136870A5071772212 @default.
• W1544136870 hasAuthorship W1544136870A5075477128 @default.
• W1544136870 hasBestOaLocation W15441368701 @default.
• W1544136870 hasConcept C142724271 @default.
• W1544136870 hasConcept C203014093 @default.
• W1544136870 hasConcept C22070199 @default.
• W1544136870 hasConcept C2777633098 @default.
• W1544136870 hasConcept C2779134260 @default.
• W1544136870 hasConcept C2779951007 @default.
• W1544136870 hasConcept C2909607560 @default.
• W1544136870 hasConcept C2994168385 @default.
• W1544136870 hasConcept C3019447875 @default.
• W1544136870 hasConcept C71924100 @default.
• W1544136870 hasConcept C86803240 @default.
• W1544136870 hasConceptScore W1544136870C142724271 @default.
• W1544136870 hasConceptScore W1544136870C203014093 @default.
• W1544136870 hasConceptScore W1544136870C22070199 @default.
• W1544136870 hasConceptScore W1544136870C2777633098 @default.
• W1544136870 hasConceptScore W1544136870C2779134260 @default.
• W1544136870 hasConceptScore W1544136870C2779951007 @default.
• W1544136870 hasConceptScore W1544136870C2909607560 @default.
• W1544136870 hasConceptScore W1544136870C2994168385 @default.
• W1544136870 hasConceptScore W1544136870C3019447875 @default.
• W1544136870 hasConceptScore W1544136870C71924100 @default.
• W1544136870 hasConceptScore W1544136870C86803240 @default.
• W1544136870 hasIssue "3" @default.
• W1544136870 hasLocation W15441368701 @default.
• W1544136870 hasLocation W15441368702 @default.
• W1544136870 hasLocation W15441368703 @default.
• W1544136870 hasLocation W15441368704 @default.
• W1544136870 hasOpenAccess W1544136870 @default.
• W1544136870 hasPrimaryLocation W15441368701 @default.
• W1544136870 hasRelatedWork W1504170807 @default.
• W1544136870 hasRelatedWork W2024812753 @default.
• W1544136870 hasRelatedWork W2060301619 @default.
• W1544136870 hasRelatedWork W2072788595 @default.
• W1544136870 hasRelatedWork W2398160926 @default.
• W1544136870 hasRelatedWork W3015231472 @default.
• W1544136870 hasRelatedWork W3165732206 @default.
• W1544136870 hasRelatedWork W3189539876 @default.
• W1544136870 hasRelatedWork W77766591 @default.
• W1544136870 hasRelatedWork W2070556937 @default.
• W1544136870 hasVolume "169" @default.
• W1544136870 isParatext "false" @default.
• W1544136870 isRetracted "false" @default.
• W1544136870 magId "1544136870" @default.
• W1544136870 workType "article" @default.