Alzheimer's disease: The amyloid hypothesis on trial

British Journal of Psychiatry

Volumn 208, Issue 1, 2016, Pages 1-3

  Harrison, Judith R ^a   Owen, Michael J ^a  

^a CARDIFF UNIVERSITY SCHOOL OF MEDICINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID; AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; BIOLOGICAL MARKER;

ALZHEIMER DISEASE; CLINICAL FEATURE; CLINICAL TRIAL (TOPIC); DISEASE MARKER; GENETIC ANALYSIS; HISTOLOGY; HUMAN; MOLECULAR GENETICS; PATHOGENESIS; PROTEIN METABOLISM; REVIEW; BRAIN; CEREBROSPINAL FLUID; DIAGNOSTIC IMAGING; GENETICS; PATHOLOGY; POSITRON EMISSION TOMOGRAPHY;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; BIOMARKERS; BRAIN; CLINICAL TRIALS AS TOPIC; HUMANS; POSITRON-EMISSION TOMOGRAPHY;

EID: 84956690809     PISSN: 00071250     EISSN: 14721465     Source Type: Journal    
DOI: 10.1192/bjp.bp.115.167569     Document Type: Review

References (22)

1. Hardy JA, Higgins GA. Alzheimer's disease: The amyloid cascade hypothesis. Science 1992; 256: 184-5.
2. Drachman DA. The amyloid hypothesis, time to move on: Amyloid is the downstream result, not cause, of Alzheimer's disease. Alzheimers Dement 2014; 10: 372-80.
3. Selkoe DJ. The molecular pathology of Alzheimer's disease. Neuron 1991; 6: 487-98.
4. Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci 1991; 12: 383-8.
5. Tanzi RE. The genetics of Alzheimer disease. Cold Spring Harb Perspect Med 2012; 2: A006296.
6. Sambamurti K, Vasudevaraju P, Mintzer J, Bachman D, Granholm C. Can the failure of Alzheimer's disease clinical trials be stepping stones to ultimate success: is the amyloid hypothesis discredited by animal models. J Alzheimers Dis Parkinsonism 2012; 2: E115.
7. Jack CR, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol 2010; 9: 119-28.
8. Rodrigue KM, Kennedy KM, Devous MD, Rieck JR, Hebrank AC, Diaz-Arrastia R, et al. b-Amyloid burden in healthy aging: Regional distribution and cognitive consequences. Neurology 2012; 78: 387-95.
9. Braak H, Braak E. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging 1997; 18: 351-7.
10. Jack CR, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer's disease: An updated hypothetical model of dynamic biomarkers. Lancet Neurol 2013; 12: 207-16.
11. Karran E, Mercken M, De Strooper B. The amyloid cascade hypothesis for Alzheimer's disease: An appraisal for the development of therapeutics. Nat Rev Drug Discov 2011; 10: 698-712.
12. Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet 2009; 41: 1088-93.
13. Doody RS, Raman R, Farlow M, Iwatsubo T, Vellas B, Joffe S, et al. A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N Engl J Med 2013; 369: 341-50.
14. Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, et al. Clinical effects of Ab immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005; 64: 1553-62.
15. Karran E, Hardy J. A critique of the drug discovery and phase 3 clinical programs targeting the amyloid hypothesis for Alzheimer disease. Ann Neurol 2014; 76: 185-205.
16. Toyn JH, Ahlijanian MK. Interpreting Alzheimer's disease clinical trials in light of the effects on amyloid-b. Alzheimers Res Ther 2014; 6: 14.
17. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011; 7: 280-92.
18. Hyman BT, Sorger P. Failure analysis of clinical trials to test the amyloid hypothesis. Ann Neurol 2014; 76: 159-61.
19. Choi SH, Kim YH, Hebisch M, Sliwinski C, Lee S, D'Avanzo C, et al. A threedimensional human neural cell culture model of Alzheimer/'s disease. Nature 2014; 515: 274-8.
20. Vellas B, Carrillo MC, Sampaio C, Brashear HR, Siemers E, Hampel H, et al. Designing drug trials for Alzheimer's disease: What we have learned from the release of the phase III antibody trials: A report from the EU/US/CTAD Task Force. Alzheimers Dement 2013; 9: 438-44.
21. Sperling RA, Rentz DM, Johnson KA, Karlawish J, Donohue M, Salmon DP, et al. The A4 study: stopping AD before symptoms begin? Sci Transl Med 2014; 6: 228.
22. Mullard A. Sting of Alzheimer's failures offset by upcoming prevention trials. Nat Rev Drug Discov 2012; 11: 657-60.