Changing the course of Alzheimer's disease: Anti-amyloid disease-modifying treatments on the horizon

Primary Care Companion to the Journal of Clinical Psychiatry

Volumn 9, Issue 1, 2007, Pages 32-41

  Christensen, Daniel D ^a  

^a University of Utah Neuropsychiatric Institute   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACC 001; ALPHA SECRETASE; ALZHEIMER DISEASE VACCINE; AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-42]; AMYLOID BETA PROTEIN[38-40]; ATORVASTATIN; BAPINEUZUMAB; BETA SECRETASE INHIBITOR; CLIOQUINOL; COLOSTRININ; DONEPEZIL; FLURBIPROFEN; FLURBIPROFEN 4 NITROXYBUTYL ESTER; GALANTAMINE; GAMMA SECRETASE INHIBITOR; HOMOTAURINE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMMUNOGLOBULIN; IMMUNOLOGIC AGENT; LEUPRORELIN; LEVO FLURBIPROFEN; LY 450139; MEMANTINE; NONSTEROID ANTIINFLAMMATORY AGENT; PBT 1; POLYPEPTIDE; QUINOLINE DERIVED ANTIINFECTIVE AGENT; RIVASTIGMINE; SIMVASTATIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VP 4896;

ABDOMINAL PAIN; ACTIVE IMMUNIZATION; ALZHEIMER DISEASE; ANEMIA; AUTOIMMUNE DISEASE; AUTOIMMUNE MENINGOENCEPHALITIS; BLOOD PRESSURE; BRAIN ATROPHY; CLINICAL TRIAL; COGNITION; COST OF ILLNESS; DAILY LIFE ACTIVITY; DRUG BLOOD LEVEL; DRUG ERUPTION; DRUG SAFETY; DRUG TARGETING; ENZYME ACTIVITY; EOSINOPHILIA; GASTROINTESTINAL HEMORRHAGE; GASTROINTESTINAL TOXICITY; GENE EXPRESSION; HIPPOCAMPUS; HUMAN; HYPOTHESIS; IMMUNOTHERAPY; LOWER RESPIRATORY TRACT INFECTION; MENINGOENCEPHALITIS; MENTAL DISEASE; NEPHROTOXICITY; NEUROFIBRILLARY TANGLE; NEUROIMAGING; NONHUMAN; OLIGOMERIZATION; PASSIVE IMMUNIZATION; PATHOPHYSIOLOGY; PROTEIN AGGREGATION; REVIEW; SENILE PLAQUE; SIDE EFFECT; TREATMENT OUTCOME; URINE INCONTINENCE;

EID: 33847093927     PISSN: 15235998     EISSN: 1555211X     Source Type: Journal    
DOI: 10.4088/pcc.v09n0106     Document Type: Review

References (91)

1. Hebert LE, Scherr PA, Scherr JL, et al. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol 2003;60:1119-1122
2. Kaduszkiewicz H, Zimmermann T, Beck-Bornholdt HP, et al. Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials. Br Med J 2005;331:321-327
3. Rosenberg RN. Translational research on the way to effective therapy for Alzheimer disease. Arch Gen Psychiatry 2005;62:1186-1192
4. Walker LC, Ibegbu CC, Todd CW, et al. Emerging prospects for the disease-modifying treatment of Alzheimer's disease. Biochem Pharmacol 2005;69:1001-1008
5. Lopez OL, Becker JT, Wisniewski S, et al. Cholinesterase inhibitor treatment alters the natural history of Alzheimer's disease. J Neurol Neurosurg Psychiatry 2002;72:310-314
6. Courtney C, Farrell D, Gray R, et al. Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial. Lancet 2004;363:2105-2115
7. Krishnan KRR, Charles HC, Doraiswamy PM, et al. Randomized, placebo-controlled trial of the effects of donepezil on neuronal markers and hippocampal volumes in Alzheimer's disease. Am J Psychiatry 2003;160:2003-2011
8. Hashimoto M, Kazui H, Matsumoto K, et al. Does donepezil treatment slow the progression of hippocampal atrophy in patients with Alzheimer's disease? Am J Psychiatry 2005;162:676-682
9. Reisberg B, Doody R, Stöffler A, et al. Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med 2003;348:1333-1341
10. Tariot PN, Farlow MR, Grossberg GT, et al. Memantine treatment in patients with moderate to severe Alzheimer's disease already receiving donepezil: a randomized controlled trial. JAMA 2004;291:317-324
11. Kirschstein R. Disease-specific estimates of direct and indirect costs of illness and NIH support. Fiscal year 2000 update. National Institutes of Health. Available at: http://ospp.od.nih.gov/ecostudies/COIreportweb.htm. Accessed Jan 22, 2006
12. Sloane PD, Zimmerman S, Suchindran C, et al. The public health impact of Alzheimer's disease, 2000-2050: potential implication of treatment advances. Annu Rev Public Health 2002;23:213-231
13. Leon J, Cheng CK, Neumann PJ. Alzheimer's disease care: costs and potential savings. Health Aff 1998;17:206-216
14. Gandy S. The role of cerebral amyloid β accumulation in common forms of Alzheimer disease. J Clin Invest 2005;115:1121-1129
15. Gandy S, Martins RN, Buxbaum J. Molecular and cellular basis for anti-amyloid therapy in Alzheimer disease. Alzheimer Dis Assoc Disord 2003;17:259-266
16. Selkoe DJ, Schenk D. Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Ann Rev Pharmacol Toxicol 2003;43:545-584
17. Cummings JL. Alzheimer's disease. N Engl J Med 2004;351:56-67
18. Hsiao K, Chapman P, Nilsen S, et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 1996;274:99-102
19. Näslund J, Haroutunian V, Mohs R, et al. Correlation between elevated levels of amyloid β peptide in the brain and cognitive decline. JAMA 2000;283:1571-1577
20. Gong Y, Chang L, Viola KL, et al. Alzheimer's disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss. PNAS 2003;100:10417-10422
21. Georganopoulou DG, Chang L, Nam J-M, et al. Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's disease. PNAS 2005;102:2273-2276
22. Oddo S, Billings L, Kesslak JP, et al. Abeta immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome. Neuron 2004;43:321-332
23. Gelinas DS, DaSilva K, Fenili D, et al. Immunotherapy for Alzheimer's disease. Proc Natl Acad Sci U S A 2004;101(suppl 2):14657-14662
24. Schenk D, Barbour R, Dunn W, et al. Immunization with amyloid-β attenuates Alzheimer disease-like pathology in the PDAPP mouse. Nature 1999;400:173-177
25. Janus C, Pearson J, McLaurin J, et al. A beta peptide immunization reduces behavioral impairment and plaques in a model of Alzheimer's disease. Nature 2000;408:979-982
26. Morgan D, Diamond DM, Gottschall PE, et al. A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 2000;408:982-985
27. 42 (AN1792) in patients with AD. Neurology 2005;64:94-101
28. Gilman S, Koller M, Black RS, et al. Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005;64:1553-1562
29. Orgogozo JM, Gilman S, Dartigues JF, et al. Subacute meningoencephalitis in a subset of patients with AD after Aβ42 immunization. Neurology 2003;61:46-54
30. Robinson SR, Bishop GM, Lee HG, et al. Lessons from the AN1792 Alzheimer vaccine: lest we forget. Neurobiol Aging 2004;25:609-615
31. Hock C, Konietzko U, Streffer JR, et al. Antibodies against beta-amyloid slow cognitive decline in Alzheimer's disease. Neuron 2003;38:547-554
32. Fox NC, Black RS, Gilman S, et al. Effects of Abeta immunotherapy (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology 2005;64:1563-1572
33. Alzforum: Drugs in Clinical Trials. ACC-001. 2005. Available at: http://www.alzforum.org/drg/drc/detail.asp?id=102. Accessed Jan 22, 2006
34. Alzforum: Drugs in Clinical Trials. AAB-001. 2005. Available at: http://www.alzforum.org/drg/drc/detail.asp?id=101. Accessed Jan 22, 2006
35. Relkin N, Szabo P, Adamiak B, et al. Intravenous immunoglobulin (IVIg) treatment causes dose-dependent alterations in B-amyloid (AB) levels and anti-AB antibody titers in plasma and cerebrospinal fluid (csf) of Alzheimer's disease (AD) patients. Neurology 2005;64(suppl 1):A144
36. Pollack SJ, Lewis H. Secretase inhibitors for Alzheimer's disease: challenges of a promiscuous protease. Curr Opin Investig Drugs 2005;6:35-47
37. Wong GT, Manfra D, Poulet FM, et al. Chronic treatment with the γ-secretase inhibitor LY-411,575 inhibits β-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem 2004;279:12876-12882
38. Wang Y, Chan SL, Miele L, et al. Involvement of Notch signaling in hippocampal synaptic plasticity. PNAS 2004;101:9458-9462
39. Saura CA, Choi S-Y, Beglopoulos V, et al. Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 2004;42:23-36
40. Siemers E, Skinner M, Dean RA, et al. Safety, tolerability, and changes in amyloid β concentrations after administration of a γ-secretase inhibitor in volunteers. Clin Neuropharmacol 2005;28:126-132
41. Siemers E, Quinn J, Kaye J, et al. Effect of LY450139, a functional γ-secretase inhibitor, on plasma and cerebrospinal fluid concentrations A-β and cognitive functioning in patients with mild to moderate Alzheimer's disease. Neurology 2004;62(suppl 5):A174
42. Alzforum: Drugs in Clinical Trials. Beta- & Gamma-secretase inhibitors. 2005. Available at: http://www.alzforum.org/drg/drc/detail.asp?id= 22. Accessed Jan 22, 2006
43. Serneels L, Dejaegere T, Craessaerts K, et al. Differential contribution of the three Aph1 genes to gamma-secretase activity in vivo. Proc Natl Acad Sci U S A 2005;102:1719-1724
44. Barten DM, Guss VL, Corsa JA, et al. Dynamics of β-amyloid reductions in brain, cerebrospinal fluid, and plasma of β-amyloid precursor protein transgenic mice treated with a γ-secretase inhibitor. J Pharmacol Exp Ther 2005;312:635-643
45. Rosenberg RN. Explaining the cause of the amyloid burden in Alzheimer disease. Arch Neurol 2002;59:1367-1368
46. Luo Y, Bolon B, Damore MA, et al. BACE1 (beta-secretase) knockout mice do not acquire compensatory gene expression changes or develop neural lesions over time. Neurobiol Dis 2003;14:81-88
47. Wong P. BACE. Alzheimer's & Dementia 2005;1(suppl 1):S3
48. Citron M. β-Secretase inhibition for the treatment of Alzheimer's disease: promise and challenge. Trends Pharmacol Sci 2004;25:92-97
49. Weggen S, Eriksen JL, Sagi SA, et al. Aβ42-lowering nonsteroidal anti-inflammatory drugs preserve intramembrane cleavage of the amyloid precursor protein (APP) and ErbB-4 receptor and signaling through the APP intracellular domain. J Biol Chem 2003;278:30748-30754
50. Beher D, Clarke EE, Wrigley JD, et al. Selected nonsteroidal antiinflammatory drugs and their derivatives target γ-secretase at a novel site: evidence for an allosteric mechanism. J Biol Chem 2004;279:43419-43426
51. 42 and change presenilin 1 conformation. Nat Med 2004;10:1065-1066
52. Townsend KP, Praticò D. Novel therapeutic opportunities for Alzheimer's disease: focus on nonsteroidal anti-inflammatory drugs. FASEB J 2005;19:1592-1601
53. 42 modifying agents: effects on Aβ deposition and behavior in Tg2576 mice. Presented at the 9th International Conference on Alzheimer's Disease and Related Disorders; July 18, 2004; Philadelphia, Pa
54. Galasko D, Graff-Radford N, Murphy MP, et al. Safety, tolerability, pharmacokinetics and Aβ levels following short-term administration of R-flurbiprofen in healthy elderly individuals: a phase 1 study. Presented at the 9th International Conference on Alzheimer's Disease and Related Disorders; July 18, 2004; Philadelphia, Pa
55. Press release. Myriad Genetics' follow-on study of Flurizan demonstrates cognitive improvement in Alzheimer's disease. Nov 15, 2005. Available at: http://www.myriad.com/news/release/051115. Accessed Jan 22, 2006
56. Gervais F, Chalifour R, Garceau D, et al. Glycosaminoglycan mimetics: a therapeutic approach to cerebral amyloid angiopathy. Amyloid 2001;8 (suppl 1):28-35
57. Garceau D, Gurbindo C, Laurin J. Safety, tolerability and pharmacokinetic profile of Alzhemed, an anti-amyloid agent for Alzheimer's disease, in healthy subjects. Presented at the 7th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy; April 3-6, 2002; Geneva, Switzerland
58. Geerts H. NC-531 Neurochem. Curr Opin Investig Drugs 2004;5:95-100
59. Aisen P, Mehran M, Poole R, et al. Clinical data on Alzhemed after 12 months of treatment in patients with mild to moderate Alzheimer's disease. Presented at the 9th International Conference on Alzheimer's Disease and Related Disorders; July 18, 2004; Philadelphia, Pa
60. Gibson GL, Douraghi-Zadeh D, Parsons RB, et al. Properties of ovine colostrinin (O-CLN) on the in vitro aggregation and toxicity of β-amyloid. Neurobiol Aging 2004;25:592
61. Rattray M. Technology evaluation: colostrinin, ReGen. Curr Opin Mol Ther 2005;7:78-84
62. Bilikiewicz A, Gaus W. Colostrinin (a naturally occurring, prolinerich, polypeptide mixture) in the treatment of Alzheimer's disease. J Alzheimer's Dis 2004;6:17-26
63. Leszek J, Inglot AD, Janusz M, et al. Colostrinin proline-rich polypeptide complex from ovine colostrum - a long-term study of its efficacy in Alzheimer's disease. Med Sci Monit 2002;8:PI93-PI96
64. Ritchie CW, Bush AI, Mackinnon A, et al. Metal-protein attenuation with iodochlorhydroxyquin (Clioquinol) targeting Aβ amyloid deposition and toxicity in Alzheimer disease. Arch Neurol 2003;60:1685-1691
65. Shaw KTY, Utsuki T, Rogers J, et al. Phenserine regulates translation of β-amyloid precursor protein mRNA by a putative interleukin-1 responsive element, a target for drug development. PNAS 2001;98:7605-7610
66. Winblad B. The efficacy of phenserine in the treatment of mild-to-moderate Alzheimer's disease. Presented at the 7th International Conference on Alzheimer's Disease and Parkinson's Disease; March 12, 2005; Sorrento, Italy
67. in't Veld BA, Ruitenberg A, Hofman A, et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. N Engl J Med 2001;345:1515-1521
68. McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies. Neurology 1996;47:425-432
69. Szekely CA, Thorne JE, Zandi PP, et al. Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer's disease: a systematic review. Neuroepidemiology 2004;23:159-169
70. Aisen PS, Schafer KA, Grundman M, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 2003;289:2819-2826
71. Reines SA, Block GA, Morris JC, et al. Rofecoxib: no effect on Alzheimer's disease in a 1-year, randomized, blinded, controlled study. Neurology 2004;62:66-71
72. Scharf S, Mander A, Ugoni A, et al. A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease. Neurology 1999;53:197-201
73. Rogers J, Kirby LC, Hempelman SR, et al. Clinical trial of indomethacin in Alzheimer's disease. Neurology 1993;43:1609-1611
74. Tabet N, Feldman H. Indomethacin for the treatment of Alzheimer's disease patients. Cochrane Database Syst Rev 2002;CD003673
75. Reynolds J, Mintzer J. Alzheimer disease update: new targets, new options. Drug Benefit Trends 2005;17:83-88;91-95
76. Press release. Use of nonsteroidal anti-inflammatory drugs suspended in large Alzheimer's disease prevention trial. NIH News. Dec 20, 2004. Available at: http://www.nih.gov/news/pr/dec2004/od-20.htm. Accessed Jan 22, 2006
77. Hauss-Wegrzyniak B, Vraniak P, Wenk GL. The effects of a novel NSAID on chronic neuroinflammation are age dependent. Neurobiol Aging 1999;20:305-313
78. Van Groen T, Kadish I. Transgenic AD model mice, effects of potential anti-AD treatments on inflammation and pathology. Brain Res Brain Res Rev 2005;48:370-378
79. Press release. NicOx announces successful phase I clinical results with HCT 1026 in development for Alzheimer's disease. May 13, 2003. Available at: http://www.nicox.com/upload/HCT%201026%20Final%20English.pdf. Accessed Jan 22, 2006
80. Fiorucci S, Santucci L, Sardina M, et al. Effect of HCT1026, a nitric oxide (NO) releasing derivative of flurbiprofen, on gastrointestinal mucosa: a double blind placebo-controlled endoscopic study. Presented at Digestive Disease Week; May 17-22, 2003; Orlando, Fla
81. Derwent Information Ltd. Nitroflurbiprofen (oral), NicOx. April 26, 2004. Available at: http://www.bizcharts.com/pdfs/IDdbCox2Record.pdf. Accessed Dec 14, 2005
82. Wolozin B, Kellman W, Ruosseau P, et al. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000;57:1439-1443
83. Sparks DL, Sabbagh MN, Connor DJ, et al. Atorvastatin therapy lowers circulating cholesterol but not free radical activity in advance of identifiable clinical benefit in the treatment of mild-to-moderate AD. Curr Alzheimer Res 2005;2:343-353
84. Pedrini S, Carter TL, Prendergast G, et al. Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK. PLoS Med. 2005;2:e18
85. ClinicalTrials.gov. ALADDIN study, phase III: antigonadotropin-leuprolide in Alzheimer's disease drug investigation (VP-AD-301). Available at: http://www.clinicaltrials.gov/ct/show/NCT00231946?order=1. Accessed Jan 22, 2006
86. Bowen RL, Verdile G, Liu T, et al. Luteinizing hormone, a reproductive regulator that modulates the processing of amyloid-β precursor protein and amyloid-β deposition. J Biol Chem 2004;279:20539-20545
87. Golde TE. Alzheimer disease therapy: can the amyloid cascade be halted? J Clin Invest 2003;111:11-18
88. Gorelick PB. Risk factors for vascular dementia and Alzheimer disease. Stroke 2004;35(suppl 1):2620-2622
89. Jorm AF. Cross-national comparisons of the occurrence of Alzheimer's and vascular dementias. Eur Arch Psychiatry Clin Neurosci 1991;240:218-222
90. Poirier J, Davignon J, Bouthillier D, et al. Apolipoprotein E polymorphism and Alzheimer's disease. Lancet 1993;342:697-699
91. Lott IT, Head E. Alzheimer disease and Down syndrome: factors in pathogenesis. Neurobiol Aging 2005;26:383-389