The Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease Trial: A study of crenezumab versus placebo in preclinical PSEN1 E280A mutation carriers to evaluate efficacy and safety in the treatment of autosomal-dominant Alzheimer's disease, including a placebo-treated noncarrier cohort

Alzheimer's and Dementia: Translational Research and Clinical Interventions

Volumn 4, Issue , 2018, Pages 150-160

  Tariot, Pierre N ^a   Lopera, Francisco ^b   Langbaum, Jessica B ^a   Thomas, Ronald G ^c   Hendrix, Suzanne ^d   Schneider, Lon S ^e   Rios Romenets, Silvia ^b   Giraldo, Margarita ^b   Acosta, Natalia ^b   Tobon, Carlos ^b   Ramos, Claudia ^b   Espinosa, Alejandro ^b   Cho, William ^f   Ward, Michael ^f   Clayton, David ^f   Friesenhahn, Michael ^f   Mackey, Howard ^f   Honigberg, Lee ^f   Sanabria Bohorquez, Sandra ^f   Chen, Kewei ^a   Walsh, Trisha ^a   Langlois, Carolyn ^a   Reiman, Eric M ^a   more..

^a BANNER ALZHEIMER S INSTITUTE   (United States)

^b UNIVERSIDAD DE ANTIOQUIA   (Colombia)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d Pentara Corporation   (United States)

^e STATE OF CALIFORNIA   (United States)

^f GENENTECH INC   (United States)

Author keywords

Alzheimer's disease; Alzheimer's Prevention Initiative; Autosomal dominant Alzheimer's disease; Clinical trial; Crenezumab; Preclinical Alzheimer's disease; Prevention

Indexed keywords

AMYLOID; AMYLOID BETA PROTEIN; APOLIPOPROTEIN E4; CRENEZUMAB; FLUORODEOXYGLUCOSE; PLACEBO; PRESENILIN 2; TAU PROTEIN;

ADULT; ALZHEIMER DISEASE; ARTICLE; AUTOSOMAL DOMINANT ALZHEIMER DISEASE; AUTOSOMAL DOMINANT INHERITANCE; CLINICAL EFFECTIVENESS; CLINICAL EVALUATION; COGNITION; COGNITIVE DEFECT; COHORT ANALYSIS; CONTROLLED STUDY; DEMENTIA; DISEASE COURSE; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; GENE MUTATION; HUMAN; MAJOR CLINICAL STUDY; MALE; MEMORY DISORDER; MILD COGNITIVE IMPAIRMENT; NUCLEAR MAGNETIC RESONANCE IMAGING; OUTCOME ASSESSMENT; PHASE 2 CLINICAL TRIAL; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; TIME TO TREATMENT; TREATMENT DURATION;

EID: 85046378959     PISSN: None     EISSN: 23528737     Source Type: Journal    
DOI: 10.1016/j.trci.2018.02.002     Document Type: Article

References (53)

1. Evans, D.A., Funkenstein, H.H., Albert, M.S., Scherr, P.A., Cook, N.R., Chown, M.J., et al. Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported. JAMA 262 (1989), 2551–2556.
2. Corrada, M.M., Brookmeyer, R., Paganini-Hill, A., Berlau, D., Kawas, C.H., Dementia incidence continues to increase with age in the oldest old: The 90+ study. Ann Neurol 67 (2010), 114–121.
3. Selkoe, D.J., Hardy, J., The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med 8 (2016), 595–608.
4. Alzheimer Disease & Frontotemporal Dementia Mutation Database. Available at: www.molgen.ua.ac.be/admutations/. Accessed March 16, 2018.
5. Kosik, K.S., Muñoz, C., Lopez, L., Arcila, M.L., García, G., Madrigal, L., et al. Homozygosity of the autosomal dominant Alzheimer disease presenilin 1 E280A mutation. Neurology 84 (2015), 206–208.
6. Bateman, R.J., Aisen, P.S., De Strooper, B., Fox, N.C., Lemere, C.A., Ringman, J.M., et al. Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease. Alzheimers Res. Ther, 2, 2011, 35.
7. Kramp, V.P., Herrling, P., List of drugs in development for neurodegenerative diseases: update June 2010. Neurodegener Dis 8 (2011), 44–94.
8. Hardy, J., Selkoe, D.J., The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297 (2002), 353–356.
9. Selkoe, D.J., Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. Behav Brain Res 192 (2008), 106–113.
10. Brookmeyer, R., Gray, S., Kawas, C., Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am J Public Health 88 (1998), 1337–1342.
11. Sperling, R.A., Aisen, P.S., Beckett, L.A., Bennett, D.A., Craft, S., Fagan, A.M., et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging and the Alzheimer's Association Workgroup. Alzheimer Dement, 7, 2011, 280.
12. Cornejo, W., Lopera, F., Uribe, C.S., Salinas, M., Descripcion de una familia con demencia presenil tipo Alzheimer. Acta Med Colombiana, 12, 1987, 55.
13. Lendon, C.L., Martinez, A., Behrens, I.M., Kosik, K.S., Madrigal, L., Norton, J., et al. E280A PS-1 mutation causes Alzheimer's disease but age of onset is not modified by ApoE alleles. Hum Mutat, 10, 1997, 186.
14. Lopera, F., Arcos, M., Madrigal, L., Kosik, K., Cornejo, W., Ossa, J., Demencia tipo Alzheimer con agregacion familiar en Antioquia, Colombia. Acta Neurol Colomb, 10, 1994, 173.
15. Lopera, F., Ardilla, A., Martínez, A., Madrigal, L., Arango-Viana, J.C., Lemere, C.A., et al. Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation. JAMA, 277, 1997, 793.
16. Acosta-Baena, N., Sepulveda-Falla, D., Lopera-Gomez, C.M., Jaramillo-Elorza, M.C., Moreno, S., Aguirre-Acevedo, D.C., et al. Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease: a retrospective cohort study. Lancet Neurol, 10, 2011, 213.
17. Arango-Lasprilla, J.C., Cuetos, F., Valencia, C., Uribe, C., Lopera, F., Cognitive changes in the preclinical phase of familial Alzheimer's disease. J Clin Exp Neuropsychol, 29, 2007, 892.
18. Fleisher, A.S., Chen, K., Quiroz, Y.T., Jakimovich, L.J., Gomez, M.G., Langois, C.M., et al. Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study. Lancet Neurol 11 (2012), 1057–1065.
19. Sepulveda-Falla, D., Matschke, J., Bernreuther, C., Hagel, C., Puig, B., Villegas, A., et al. Deposition of hyperphosphorylated tau in cerebellum of PS1 E280A Alzheimer's disease. Brain Pathol 21 (2011), 452–463.
20. Quiroz, Y., Sperling, R., Lopera, F., Fleisher, A., Chen, K., Tirado, V., et al. Task-dependent fMRI abnormalities in young adults at genetic risk for early-onset Alzheimer's disease. Alzheimers Dement 7 (2011), S219–S220.
21. Fleisher, A., Quiroz, Y., Chen, K., Langbaum, J.B., Thiyyagura, P., Liu, X., et al. Reduced regional gray matter in cognitively normal young adults at genetic risk for early-onset Alzheimer's disease. Alzheimers Dement, 7, 2011, S232.
22. Reiman, E.M., Velez-Pardo, C., Jimenez del Rio, M., Giraldo, M., Acosta-Baena, N., Kosik, K., et al. Elevated cerebrospinal fluid amyloid-Beta42 levels in young adults at genetic risk for early-onset Alzheimer's disease. Alzheimers Dement 7 (2011), S102–S103.
23. Ayutyanont, N., Lopera, F., Hendrix, S., Langbaum, J.B., Madrigal, L., Moreno, S., et al. Composite cognitive endpoints with improved power to detect presymptomatic Alzheimer's disease treatment effects: findings in the Colombian kindred with the E280A Presenilin 1 mutation and the Alzheimer's Prevention Initiative. Alzheimers Dement, 7, 2011, S608.
24. Ultsch, M., Li, B., Maurer, T., Mathieu, M., Adolfsson, O., Muhs, A., et al. Structure of crenezumab complex with Aβ shows loss of β-hairpin. Sci Rep, 6, 2016, 39374.
25. Adolfsson, O., Pihlgren, M., Toni, N., Varisco, Y., Buccarello, A.L., Antoniello, K., et al. An effector-reduced anti-β-amyloid (Aβ) antibody with unique aβ binding properties promotes neuroprotection and glial engulfment of Aβ. J Neurosci 32 (2012), 9677–9689.
26. Sperling, R.A., Jack, C.R. Jr., Black, S.E., Frosch, M.P., Greenberg, S.M., Hyman, B.T., et al. Amyloid related imaging abnormalities in amyloid modifying therapeutic trials: recommendations from the Alzheimer's Association Research Roundtable Workgroup. Alzheimers Dement 7 (2011), 367–385.
27. Wilcock, D.M., Alamed, J., Gottschall, P.E., Grimm, J., Rosenthal, A., Pons, J., et al. Deglycosylated anti-amyloid-beta antibodies eliminate cognitive deficits and reduce parenchymal amyloid with minimal vascular consequences in aged amyloid precursor protein transgenic mice. J Neurosci 26 (2006), 5340–5346.
28. Cummings, J., Cho, W., Ward, M., Friesenhahn, M., Brunstein, F., Honigberg, L., et al. A randomized, double-blind, placebo-controlled phase 2 study to evaluate the efficacy and safety of crenezumab in patients with mild to moderate Alzheimer's diseases. Alzheimers Dement, 10, 2014, P275 Alzheimer's Association International Conference oral presentation.
29. Salloway, S., Cho, W., Clayton, D., Honigberg, L., Rabe, C., Friesenhahn, M., et al. Amyloid PET imaging results from a study to evaluate the impact of crenezumab on fibrillar amyloid in patients with mild-to-moderate Alzheimer's disease. J Prev Alz 1 (2014), 214–296.
30. Reiman, E.M., Chen, K., Cho, W., Clayton, D., Honigberg, L., Rabe, C., et al. Analysis of amyloid-β PET changes from the crenezumab anti-Aβ phase 2 trial using a pre-specified cerebral white matter reference region-of-interest. J Prev Alz 1 (2014), 214–296.
31. Chan, A.W., Tetzlaff, J.M., Gøtzsche, P.C., Altman, D.G., Mann, H., Berlin, J.A., et al. 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ, 346, 2013, e7586.
32. Chan, A.W., Tetzlaff, J.M., Altman, D.G., Laupacis, A., Gøtzsche, P.C., Krleža-Jerić, K., et al. 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med 158 (2013), 200–207.
33. Albert, M.S., DeKosky, S.T., Dickson, D., Dubois, B., Feldman, H.H., Fox, N.C., et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging and Alzheimer's Association Workgroup. Alzheimers Dement 7 (2011), 270–279.
34. McKhann, G.M., Knopman, D.S., Chertkow, H., Hyman, B.T., Jack, C.R. Jr., Kawas, C.H., et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging and the Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7 (2011), 263–269.
35. Rosen, W.G., Mohs, R.C., Davis, K.L., A new rating scale for Alzheimer's disease. Am J Psychiatry 141 (1984), 1356–1364.
36. Morris, J.C., Heyman, A., Mohs, R.C., Hughes, J.P., van Belle, G., Fillenbaum, G., et al., the CERAD investigators. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology 39 (1989), 1159–1165.
37. Mohs, R.C., Knopman, D., Petersen, R.C., Ferris, S.H., Ernesto, C., Grundman, M., et al. Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer's Disease Assessment Scale that broaden its scope. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord 11:Suppl 2 (1997), S13–S21.
38. Gollan, T.H., Weissberger, G.H., Runnqvist, E., Montoya, R.I., Cera, C.M., Self-ratings of spoken language dominance: a Multilingual Naming Test (MINT) and preliminary norms for young and aging Spanish-English bilinguals. Biling (Camb Engl) 15 (2012), 594–615.
39. Folstein, M.F., Folstein, S.E., McHugh, P.R., Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12 (1975), 189–198.
40. Raven, J., Raven Progressive Matrices. 1976, The Psychological Corporation, Toronto, Canada.
41. Morris, J.C., The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 43 (1993), 2412–2414.
42. Armitage, S., Analysis of certain psychological tests used for the evaluation of brain damage. Psychol Monogr 60 (1946), 1–277.
43. Randolph, C., Tierney, M.C., Mohr, E., Chase, T.N., The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol 20 (1998), 310–319.
44. Grober, E., Buschke, H., Genuine memory deficits in dementia. Dev Neuropsychol 3 (1987), 13–36.
45. Cummings, J.L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D.A., Gornbein, J., The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 44 (1994), 2308–2314.
46. Cummings, J.L., The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology 48 (1997), S10–S16.
47. Sheikh, J.I., Yesavage, J.A., Geriatric Depression Scale (GDS). Recent evidence and development of a shorter version. Brink, T.L., (eds.) Clinical Gerontology: A Guide to Assessment and Intervention, 1986, The Haworth Press, Inc., NY, 165–173.
48. Sclan, S.G., Reisberg, B., Functional assessment staging (FAST) in Alzheimer's disease: reliability, validity, and ordinality. Int Psychogeriatr 4:Suppl 1 (1992), 55–69.
49. Ayutyanont, N., Langbaum, J.B., Hendrix, S.B., Chen, K., Fleisher, A.S., Friesenhahn, M., et al. The Alzheimer's prevention initiative composite cognitive test score: sample size estimates for the evaluation of preclinical Alzheimer's disease treatments in presenilin 1 E280A mutation carriers. J Clin Psychiatry 75 (2014), 652–660.
50. Langbaum, J.B., Hendrix, S.B., Ayutyanont, N., Chen, K., Fleisher, A.S., Shah, R.C., et al. An empirically derived composite cognitive test score with improved power to track and evaluate treatments for preclinical Alzheimer's disease. Alzheimers Dement 10 (2014), 666–674 Epub 2014 Apr 21.
51. Kozauer, N., Katz, R., Regulatory innovation and drug development for early-stage Alzheimer's disease. N Engl J Med 368 (2013), 1169–1171.
52. Reiman, E.M., Langbaum, J.B., Tariot, P.N., Lopera, F., Bateman, R.J., Morris, J.C., et al. CAP–advancing the evaluation of preclinical Alzheimer disease treatments. Nat Rev Neurol 12 (2016), 56–61 Epub 2015 Sep 29.
53. Weninger, S., Carrillo, M.C., Dunn, B., Aisen, P.S., Bateman, R.J., Kotz, J.D., et al. Collaboration for Alzheimer's prevention: principles to guide data and sample sharing in preclinical Alzheimer's disease trials. Alzheimers Dement 12 (2016), 631–632.