investigational therapies for treatment of Alzheimer's disease

From Aaushi
Jump to navigation Jump to search

Comparative biology

in vitro studies

studies in rodents

studies in humans

conjugated nanoparticles

* magnetic nanoparticles can efficiently cross the blood-brain barrier ** the 7-D-peptide can self-aggregate forming a right-handed fibril

  • upon binding to tau fibrils, the 7-D-peptide initially conforms to the left-handed twist of tau fibrils
  • however, the 7-D-peptide reverses its twist to relieve the torsional strain & by doing so disrupts the tau fibril, enabling its fragmentation[90]
  • fragments produced after the 7-D-peptide disassembles tau fibrils do not seed the growth of new tau fibrils[90]

gene transfer studies in humans

genomic analysis of the human proteome

sensory stimulation

  • a device that delivers a combination of auditory & visual stimulations at a frequency of 40 Hertz (Hz) elicits gamma oscillation in the brain as recorded by EEG
    • beneficial effects in cognitive & functional abilities & a reduction in brain atrophy[79]

transcranial electromagnetic stimulation

low-intensity focused ultrasound

plasma exchange

other agents

herbal therapy

gum disease

in silico

More general terms

Additional terms

References

  1. Jump up to: 1.0 1.1 Journal Watch 19:128, 1999 Schenk D et al Immunization with amyloid-beta attenuates Alzheimer-disease- like pathology in the PDAPP mouse. Nature 400:173, 1999 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10408445
  2. Jump up to: 2.0 2.1 Journal Watch 20:147, 2000 Cannon BF et al Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nature Med 6:916, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10932230
  3. Jump up to: 3.0 3.1 Chen G et al A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer's disease. Nature 408:975, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11140684
    Pearson JC et al A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature 408:979, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11140685
    Morgan D A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 408:982, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11140686
  4. Jump up to: 4.0 4.1 Marx J. Alzheimer's disease. Bad for the heart, bad for the mind? Science 294:508, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11641483
  5. Jump up to: 5.0 5.1 5.2 Journal Watch 21(24):193, 2001 in 't Veld et al Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. NEJM 345:1515,2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11794217
  6. Jump up to: 6.0 6.1 6.2 6.3 Journal Watch 21(24):194, 2001 Weggen S et al A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature 414:212, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11700559
  7. Jump up to: 7.0 7.1 7.2 7.3 Cole G., GRECC, VA Medical Center, Sepulveda, (unpublished)
    Calon F, Lim GP, Morihara T, Yang F, Ubeda O, Salem N Jr, Frautschy SA, Cole GM. Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease. Eur J Neurosci. 2005 Aug;22(3):617-26. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/16101743
  8. Jump up to: 8.0 8.1 <Internet> http://www.alz.org
  9. Jump up to: 9.0 9.1 9.2 9.3 Journal Watch 23(14):109, 2003
    Alsen PS et al Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 289:2819, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12783912
    Launer IJ Nonsteroidal anti-inflammatory drugs and Alzheimer disease: what's next? JAMA 289:2865, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12783919
  10. Jump up to: 10.0 10.1 Journal Watch 23(18):145, 2003 Etminan M et al Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies. BMJ 327:128, 2003 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/12869452 <Internet> http://bmj.com/cgi/content/full/327/7407/128
  11. Jump up to: 11.0 11.1 Rees T, Hammond PI, Soreq H, Younkin S, Brimijoin S. Acetylcholinesterase promotes beta-amyloid plaques in cerebral cortex. Neurobiol Aging. Oct;24(6):777-87. 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12927760
  12. Jump up to: 12.0 12.1 Permanne B et al Reduction of amyloid load and cerebral damage in a transgenic mouse model of Alzheimer's disease by treatment with a beta-sheet breaker peptide. FASEB J. 2002 Jun;16(8):860-2. Epub 2002 Apr 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11967228
  13. Jump up to: 13.0 13.1 13.2 13.3 Weggen S et al, Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid beta 42 production by direct modulation of gamma-secretase activity. J Biol Chem. 2003 Aug 22;278(34):31831-7. Epub 2003 Jun 12. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12805356
  14. Jump up to: 14.0 14.1 14.2 14.3 Eriksen JL et al, NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. J Clin Invest. 2003 Aug;112(3):440-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12897211
  15. Takahashi Y et al, Sulindac sulfide is a noncompetitive gamma-secretase inhibitor that preferentially reduces Abeta 42 generation. J Biol Chem. 2003 May 16;278(20):18664-70. Epub 2003 Mar 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12637581
  16. Jump up to: 16.0 16.1 Vega GL et al Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease. Arch Neurol. 2003 Apr;60(4):510-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12707064
  17. Jump up to: 17.0 17.1 Fassbender K, Simons M, Bergmann C, Stroick M, Lutjohann D, Keller P, Runz H, Kuhl S, Bertsch T, von Bergmann K, Hennerici M, Beyreuther K, Hartmann T. Simvastatin strongly reduces levels of Alzheimer's disease beta-amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5856-61. Epub 2001 Apr 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11296263
    Hoglund K, Wiklund O, Vanderstichele H, Eikenberg O, Vanmechelen E, Blennow K. Plasma levels of beta-amyloid(1-40), beta-amyloid(1-42), and total beta-amyloid remain unaffected in adult patients with hypercholesterolemia after treatment with statins. Arch Neurol. 2004 Mar;61(3):333-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15023808
  18. Jump up to: 18.0 18.1 Zandi PP et al, Arch Neurol 6:18, 2004 http://archneur.ama-assn.org/cgi/content/abstract/61/1/82
  19. Jump up to: 19.0 19.1 Journal Watch 24(24):184, 2004 Gestwicki JE, Crabtree GR, Graef IA. Harnessing chaperones to generate small-molecule inhibitors of amyloid beta aggregation. Science. 2004 Oct 29;306(5697):865-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15514157
  20. Jump up to: 20.0 20.1 Journal Watch 24(24):184, 2004 Hutter-Paier B, Huttunen HJ, Puglielli L, Eckman CB, Kim DY, Hofmeister A, Moir RD, Domnitz SB, Frosch MP, Windisch M, Kovacs DM. The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer's disease. Neuron. 2004 Oct 14;44(2):227-38. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15473963
  21. Jump up to: 21.0 21.1 Sparks DL, Sabbagh MN, Connor DJ, Lopez J, Launer LJ, Browne P, Wasser D, Johnson-Traver S, Lochhead J, Ziolwolski C. Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results. Arch Neurol. 2005 May;62(5):753-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15883262
  22. Jump up to: 22.0 22.1 22.2 22.3 O'Toole M et al Risk factors associated with beta-amyloid(1-42) immunotherapy in preimmunization gene expression patterns of blood cells Arch of Neurol 62:1513, 2005
  23. Jump up to: 23.0 23.1 McGeer EG, McGeer PL. Abeta immunotherapy and other means to remove amyloid. Curr Drug Targets CNS Neurol Disord. 2005 Oct;4(5):569-73. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16266289
  24. Jump up to: 24.0 24.1 Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides. J Biol Chem. 2005 Nov 11;280(45):37377-82. Epub 2005 Sep 14. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16162502
  25. Jump up to: 25.0 25.1 Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest. 2005 Oct;115(10):2774-83. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16151530
  26. Jump up to: 26.0 26.1 Court JA, Johnson M, Religa D, Keverne J, Kalaria R, Jaros E, McKeith IG, Perry R, Naslund J, Perry EK. Attenuation of Abeta deposition in the entorhinal cortex of normal elderly individuals associated with tobacco smoking. Neuropathol Appl Neurobiol. 2005 Oct;31(5):522-35. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16150123
  27. Jump up to: 27.0 27.1 Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM. Phenolic anti-inflammatory antioxidant reversal of Abeta- induced cognitive deficits and neuropathology. Neurobiol Aging. 2001 Nov-Dec;22(6):993-1005. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11755008
    Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001 Nov 1;21(21):8370-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11606625
  28. Jump up to: 28.0 28.1 Jankowsky JL et al, Persistent amyloidosis following suppression of Abeta production in a transgenic modell of Alzheimer disease PLoS Med 2005; Dec, 2:e355 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16279840
  29. Jump up to: 29.0 29.1 McLaurin J, Kierstead ME, Brown ME, Hawkes CA, Lambermon MH, Phinney AL, Darabie AA, Cousins JE, French JE, Lan MF, Chen F, Wong SS, Mount HT, Fraser PE, Westaway D, George-Hyslop PS. Cyclohexanehexol inhibitors of Abeta aggregation prevent and reverse Alzheimer phenotype in a mouse model. Nat Med. 2006 Jul;12(7):801-8. Epub 2006 Jun 11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16767098
  30. Jump up to: 30.0 30.1 30.2 Caccamo A et al, M1 receptors play a central role in modulating AD-like pathology in transgenic mice Neuron 2006, 49:671 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16504943
  31. Jump up to: 31.0 31.1 31.2 ADAP Research Group, Lykestos CG et al Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial. Neurology 2007, 68:1800 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17460158
  32. Jump up to: 32.0 32.1 Hartman RE, Shah A, Fagan AM, Schwetye KE, Parsadanian M, Schulman RN, Finn MB, Holtzman DM. Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease. Neurobiol Dis. 2006 Dec;24(3):506-15. Epub 2006 Sep 28. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17010630
  33. Jump up to: 33.0 33.1 Wang J, Ho L, Zhao Z, Seror I, Humala N, Dickstein DL, Thiyagarajan M, Percival SS, Talcott ST, Pasinetti GM. Moderate consumption of Cabernet Sauvignon attenuates Abeta neuropathology in a mouse model of Alzheimer's disease. FASEB J. 2006 Nov;20(13):2313-20. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17077308
  34. Jump up to: 34.0 34.1 Qin W, Yang T, Ho L, Zhao Z, Wang J, Chen L, Zhao W, Thiyagarajan M, MacGrogan D, Rodgers JT, Puigserver P, Sadoshima J, Deng H, Pedrini S, Gandy S, Sauve AA, Pasinetti GM. Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J Biol Chem. 2006 Aug 4;281(31):21745-54. Epub 2006 Jun 2. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16751189
  35. Jump up to: 35.0 35.1 Sagare A et al, Clearance of amyloid-beta by circulating lipoprotein receptors Nat Med 2007, 13:1029 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17694066
  36. Jump up to: 36.0 36.1 Wang J et al Valsartan lowers brain b-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease Journal of Clinical Investigation http://www.jci.org http://www.pubmedcentral.nih.gov/picrender.fcgi?doi=10.1172/JCI31547&blobtype=pdf PMID: https://www.ncbi.nlm.nih.gov/pubmed/17965777
  37. Jump up to: 37.0 37.1 Wang J, Ho L, Qin W, Rocher AB, Seror I, Humala N, Maniar K, Dolios G, Wang R, Hof PR, Pasinetti GM. Caloric restriction attenuates beta-amyloid neuropathology in a mouse model of Alzheimer's disease. FASEB J. 2005 Apr;19(6):659-61. Epub 2005 Jan 13. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15650008
  38. Jump up to: 38.0 38.1 Rajendran L et al, Efficient inhibition of the Alzheimer's disease beta-secretase by membrane targeting. Science 2008, 320:520 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18436784
  39. Jump up to: 39.0 39.1 39.2 39.3 Vlad SC et al. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology 2008 May 6; 70:1672 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18458226
  40. Jump up to: 40.0 40.1 Aisen PS et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: A randomized controlled trial. JAMA 2008 Oct 15; 300:1774. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18854539
    Clarke RJ and Bennett DA. B vitamins for prevention of cognitive decline: Insufficient evidence to justify treatment. JAMA 2008 Oct 15; 300:1819. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18854547
  41. Jump up to: 41.0 41.1 Green RC et al. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: A randomized controlled trial. JAMA 2009 Dec 16; 302:2557. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20009055
    Montine TJ and Larson EB. Late-life dementias: Does this unyielding global challenge require a broader view? JAMA 2009 Dec 16; 302:2593. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20009062
  42. Jump up to: 42.0 42.1 Arendasha GW et al Electromagnetic Field Treatment Protects Against and Reverses Cognitive Impairment in Alzheimer's Disease Mice Journal of Alzheimer's Disease (preprint Jan 2010) http://iospress.metapress.com/content/d6r1371722422hg2/fulltext.pdf DOI:http://dx.doi.org/ 10.3233/JAD-2009-1228
  43. Jump up to: 43.0 43.1 Quinn JF et al Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease JAMA. 2010;304(17):1903-1911 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21045096 <Internet> http://jama.ama-assn.org/cgi/content/full/304/17/1903
  44. Jump up to: 44.0 44.1 Hooshmand B et al Homocysteine and holotranscobalamin and the risk of Alzheimer disease: A longitudinal study. Neurology 2010 Oct 19; 75:1408. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20956786
  45. Jump up to: 45.0 45.1 Craft S et al Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment Arch Neurol. Published online September 12, 2011 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21911655 <Internet> http://archneur.ama-assn.org/cgi/content/full/archneurol.2011.233
    Craft S et al. Safety, efficacy, and feasibility of intranasal insulin for the treatment of mild cognitive impairment and Alzheimer disease dementia: A randomized clinical trial. JAMA Neurol 2020 Jun 22; PMID: https://www.ncbi.nlm.nih.gov/pubmed/32568367 Free PMC article https://jamanetwork.com/journals/jamaneurology/fullarticle/2767376
  46. Jump up to: 46.0 46.1 46.2 Galasko DR et al. Antioxidants for Alzheimer disease: A randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 2012 Mar 19 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22431837 <Internet> http://archneur.ama-assn.org/cgi/content/abstract/archneurol.2012.85v1
  47. Cummings JL and Zhong K Beraxotene for Alzheimer's disease: Innovative Clinical Trial Could Open the Door to Disease-Modifying Therapy. Cleveland Clinic: Neurosciences Pathways. CLEVELANDCLINIC.ORG/NEUROSCIENCE
  48. Jump up to: 48.0 48.1 Salloway S et al Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease. N Engl J Med 2014; 370:322-333. January 23, 2014 http://www.nejm.org/doi/full/10.1056/NEJMoa1304839 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24450891
    Doody RS et al Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease. N Engl J Med 2014; 370:311-321. January 23, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/4450890 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1312889
    Honig LS, Vellas B, Woodward M et al Trial of Solanezumab for Mild Dementia Due to Alzheimer's Disease. N Engl J Med 2018; 378:321-330. Jan 25, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29365294 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1705971
  49. Jump up to: 49.0 49.1 Klyubin I et al. Peripheral administration of a humanized anti-PrP antibody blocks Alzheimer's disease Abeta synaptotoxicity. J Neurosci 2014 Apr 30; 34:6140 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/2479018 <Internet> http://www.jneurosci.org/content/34/18/6140
  50. Jump up to: 50.0 50.1 Xu J, Chatterjee M, Baguley TD, Brouillette J, Kurup P, et al. Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease. PLoS Biol (2014) 12(8): e1001923 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25093460 <Internet> http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001923
  51. Jump up to: 51.0 51.1 Leinenga G, Gotz J Scanning ultrasound removes amyloid-beta and restores memory in an Alzheimer's disease mouse model. Sci Transl Med 11 March 2015: Vol. 7, Issue 278, p. 278ra33 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25761889 <Internet> http://stm.sciencemag.org/content/7/278/278ra33
  52. Jump up to: 52.0 52.1 52.2 Torro J Is Etanercept Safe and Well Tolerated in Alzheimer Disease? NEJM Journal Watch. May 27, 2015 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
    Butchart J et al. Etanercept in Alzheimer disease: A randomized, placebo- controlled, double-blind, phase 2 trial. Neurology 2015 May 26; 84:2161 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25934853 <Internet> http://www.neurology.org/content/84/21/2161
  53. Jump up to: 53.0 53.1 Kim HY, Kim HV, Jo S et al EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-beta oligomers and plaques. Nature Communications 6, Article number: 8997 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26646366 <Internet> http://www.nature.com/ncomms/2015/151208/ncomms9997/abs/ncomms9997.html
  54. Jump up to: 54.0 54.1 EurekAlert. Oct 24, 2016 Phase 3 analyses in Alzheimer's show clinical benefit of tramiprosate in APOE4 carriers https://www.eurekalert.org/pub_releases/2016-10/tyn-p3102416.php
  55. Jump up to: 55.0 55.1 Sevigny J, Chiao P, Bussiere T et al The antibody aducanumab reduces Abeta plaques in Alzheimer's disease. Nature. 2016 Aug 31;537(7618):50-6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27582220
    Reiman EM Alzheimer's disease: Attack on amyloid-beta protein. Nature. 2016 Aug 31;537(7618):36-7. doi:http://dx.doi.org/ 10.1038/537036a. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27582214
  56. Jump up to: 56.0 56.1 Gauthier S et al. Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: A randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet 2016 Nov 15; 388:2873. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27863809 Free PMC Article
    Rafii MS. Targeting tau protein in Alzheimer's disease. Lancet 2016 Nov 15; 388:2842 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27863808
  57. Jump up to: 57.0 57.1 Relkin NR, Thomas RG, Rissman RA et al. A phase 3 trial of IV immunoglobulin for Alzheimer disease. Neurology 2017 Apr 5 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28381506 <Internet> http://www.neurology.org/content/88/18/1768
  58. Jump up to: 58.0 58.1 58.2 George J. No Cognitive Benefit in Alzheimer's Gene Transfer Trial. AAV2-NGF injections give same results as sham treatment. MedPage Today. March 26, 2018 https://www.medpagetoday.com/neurology/alzheimersdisease/71992
    Rafii MS, Tuszynski MH, Thomas RG, et al Adeno-Associated Viral Vector (Serotype 2)-Nerve Growth Factor for Patients With Alzheimer Disease. A Randomized Clinical Trial. JAMA Neurol. Published online March 26, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29582053 https://jamanetwork.com/journals/jamaneurology/article-abstract/2675302
    Honig LS Gene Therapy in Alzheimer Disease - It May Be Feasible, But Will It Be Beneficial? JAMA Neurol. Published online March 26, 2018. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29582049 https://jamanetwork.com/journals/jamaneurology/article-abstract/2675299
  59. Jump up to: 59.0 59.1 Egan MF, Kost J, Tariot PN et al Randomized Trial of Verubecestat for Mild-Moderate Alzheimer's Disease. N Engl J Med 2018; 378:1691-1703. May 3, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29719179 https://www.nejm.org/doi/full/10.1056/NEJMoa1706441
  60. Jump up to: 60.0 60.1 Biogen Inc. Phase II clinical trial (Study 201) of BAN2401 Alzheimer's Association International Conference 2018
  61. Jump up to: 61.0 61.1 61.2 Martorell AJ, Paulson AL, Suk HJ et al. Multi-sensory gamma stimulation ameliorates Alzheimer's-associated pathology and improves cognition. Cell 2019 Apr 4; 177:256. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30879788 https://www.cell.com/cell/fulltext/S0092-8674(19)30163-1
  62. Jump up to: 62.0 62.1 62.2 EurekAlert News Release Sept 17, 2019 Alzheimer's memory loss reversed by new head device using electromagnetic waves. https://eurekalert.org/pub_releases/2019-09/ip-am091719.php
    Arendash G Cao C, Abulaban H et al A Clinical Trial of Transcranial Electromagnetic Treatment in Alzheimer's Disease: Cognitive Enhancement and Associated Changes in Cerebrospinal Fluid, Blood, and Brain Imaging. Journal of Alzheimer's Disease, 71(1):57-82, 2019 https://content.iospress.com/articles/journal-of-alzheimers-disease/jad190367
  63. Jump up to: 63.0 63.1 Wilson EN, Do Carmo S, Welikovitch LA et al NP03, a Microdose Lithium Formulation, Blunts Early Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats. Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 723-739, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31868669 https://content.iospress.com/articles/journal-of-alzheimers-disease/jad190862
  64. George J Alzheimer's Markers Altered With Cancer Drug -Early nilotinib study suggests it has potential to be a disease-modifying drug. MedPage Today May 29, 2020 https://www.medpagetoday.com/neurology/alzheimersdisease/86770
    Nackerdien Z Cancer Drug Nilotinib Changes Alzheimer's Disease Biomarkers - his may be a first step towards a disease-modifying treatment, phase II study suggests. MedPage Today 2020-06-18 https://www.medpagetoday.org/neurology/alzheimersdisease/87151
    Turner RS, Hebron ML, Lawler A et al Nilotinib Effects on Safety, Tolerability, and Biomarkers in Alzheimer's Disease. Ann Neurol 2020. May 28 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32468646 https://onlinelibrary.wiley.com/doi/full/10.1002/ana.25775
  65. Jump up to: 65.0 65.1 Cassava Sciences. Sept 14, 2020 Cassava Sciences Announces Final Results of a Phase 2b Clinical Study of Sumifilam in Patients with Alzheimer's Disease. https://www.globenewswire.com/news-release/2020/09/14/2092861/0/en/Cassava-Sciences-Announces-Final-Results-of-a-Phase-2b-Clinical-Study-of-Sumifilam-in-Patients-with-Alzheimer-s-Disease.html
  66. Jump up to: 66.0 66.1 66.2 Anderson P Plasma Exchange 'Encouraging' as Novel Alzheimer's Treatment Medscape - Jul 31, 2020. https://www.medscape.com/viewarticle/934937
  67. Jump up to: 67.0 67.1 Rodriguez S, Hug C, Todorov P et al Machine learning identifies candidates for drug repurposing in Alzheimer's disease. Nat Commun 12, 1033 (2021) PMID: https://www.ncbi.nlm.nih.gov/pubmed/33589615 PMCID: PMC7884393 Free PMC article https://www.nature.com/articles/s41467-021-21330-0
  68. Jump up to: 68.0 68.1 George J Marrow Cell Stimulator to Treat Alzheimer's s Disease?
    Unusual approach pans out in mid-stage trial. MedPage Today March 24, 2021 https://www.medpagetoday.com/neurology/alzheimersdisease/91795
    Potter H et al Safety and efficacy of sargramostim (GM-CSF) in the treatment of Alzheimer's disease. Alzheimer's & Dementia. 2021. March 24. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33778150 PMCID: PMC7988877 Free PMC article https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/trc2.12158
  69. Jump up to: 69.0 69.1 69.2 Monaco K Could a Food Preservative Slow Cognitive Decline in Dementia Patients?
    Post hoc data of negative trial suggested women may see benefit from sodium benzoate. MedPage Today April 21, 2021 https://www.medpagetoday.com/psychiatry/dementia/92197
    Lin CH, Chen PK, Wang SH, Lane HY Effect of sodium benzoate on cognitive function among patients with behavioral and psychological symptoms of dementia. JAMA Netw Open. 2021;4(4):e216156 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33881530 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779038
  70. Jump up to: 70.0 70.1 70.2 George J Investigational Alzheimer's Drug Shows Effects in Inherited Early-Onset Disease MedPage Today June 21,2021 https://www.medpagetoday.com/neurology/alzheimersdisease/93193
    Salloway S. et al. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease Nature Medicine (2021) PMID: https://www.ncbi.nlm.nih.gov/pubmed/34155411 https://www.nature.com/articles/s41591-021-01369-8
  71. Jump up to: 71.0 71.1 Yang T, Dang Y, Ostaszewski B, Mengel D et al Target engagement in an alzheimer trial: Crenezumab lowers amyloid beta oligomers in cerebrospinal fluid Ann Neurol. 2019 Aug;86(2):215-224 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31168802 Free PMC article Clinical Trial.
  72. Jump up to: 72.0 72.1 Yang C, Farias FHG, Ibanez L et al Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders. Nat Neurosci 2021. July 8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34239129 https://www.nature.com/articles/s41593-021-00886-6
  73. Jump up to: 73.0 73.1 Anderson P Low-Intensity Focused Ultrasound Safe, Effective in Mild Alzheimer's Disease. Medscape. August 30, 2021 https://www.medscape.com/viewarticle/957487
  74. Jump up to: 74.0 74.1 Shapira R, Efrati S, Ashery U. Hyperbaric oxygen therapy as a new treatment approach for Alzheimer's disease. Neural Regen Res. 2018 May;13(5):817-818. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29863011 Free PMC article. No abstract available.
    Shapira R, Gdalyahu A, Gottfried I et al Hyperbaric oxygen therapy alleviates vascular dysfunction and amyloid burden in an Alzheimer's disease mouse model and in elderly patients. Aging (Albany NY). 2021 Sep 9;13(17):20935-20961. Epub 2021 Sep 9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34499614 Free PMC article.
  75. Jump up to: 75.0 75.1 Li Z, Zhao N A water pill against Alzheimer's disease. Nat Aging 2021. 1, 868-869 News & Views https://www.nature.com/articles/s43587-021-00124-5
    Taubes A, Nova P, Zalocusky KA et al Experimental and real-world evidence supporting the computational repurposing of bumetanide for APOE4-related Alzheimer's disease. Nat Aging 2021. 1, 932-947 Not indexed in PubMed https://www.nature.com/articles/s43587-021-00122-7
  76. Jump up to: 76.0 76.1 Boada M, Lopez OL, Olazaran J et al Neuropsychological, neuropsychiatric, and quality-of-life assessments in Alzheimer's disease patients treated with plasma exchange with albumin replacement from the randomized AMBAR study. Alzheimer's & Dementia. 2021. Nov 2 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34726348 https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12477
  77. Jump up to: 77.0 77.1 Anderson P Lecanemab Effective in Clearing Amyloid in Early Alzheimer's. Medscape. November 23, 2021 https://www.medscape.com/viewarticle/963516
  78. Jump up to: 78.0 78.1 George J Can Viagra Prevent Alzheimer's? Sildenafil shows potential for drug repurposing MedPage Today December 6, 2021 https://www.medpagetoday.com/neurology/alzheimersdisease/96018
    Fang J, Zhang P, Zhou Y et al Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease. Nat Aging (2021) Not indexed in PubMed https://www.nature.com/articles/s43587-021-00138-z
  79. Jump up to: 79.0 79.1 Anderson P Sensory Stimulation Promising for Alzheimer's Disease. Medscape. November 15, 2021 https://www.medscape.com/viewarticle/963003
  80. Jump up to: 80.0 80.1 Anderson P Gum Disease Bacteria a New Treatment Target for Alzheimer's? Medscape. November 23, 2021 https://www.medscape.com/viewarticle/963574
  81. Jump up to: 81.0 81.1 Brooks M Novel Light Therapy Helmet Boosts Brain Function. Medscape. October 21, 2021 https://www.medscape.com/viewarticle/961326
  82. Whitlock Burton K Experimental Drug May Boost Executive Function in Alzheimer's Medscape. March 31, 2022 https://www.medscape.com/viewarticle/971365
  83. Jump up to: 83.0 83.1 Teng E, Manser PT, Pickhorn K et al Safety and Efficacy of Semorinemab in Individuals With Prodromal to Mild Alzheimer Disease. A Randomized Clinical Trial. JAMA Neurol. Published online June 13, 2022 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35696185 https://jamanetwork.com/journals/jamaneurology/fullarticle/2793069
  84. Jump up to: 84.0 84.1 Geroge J ADHD Drugs May Treat Alzheimer's Cognitive Symptoms Effectively. Positive effect on global cognition, apathy in meta-analysis. MedPage Today July 5, 2022 https://www.medpagetoday.com/neurology/alzheimersdisease/99583
    David MCB, Del Giovane M, Liu KY et al Cognitive and neuropsychiatric effects of noradrenergic treatment in Alzheimer's disease: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2022. July 5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35790417 https://jnnp.bmj.com/content/early/2022/05/31/jnnp-2022-329136
  85. Jump up to: 85.0 85.1 Zheng X, Tang Y, Yang Q et al Effectiveness and safety of anti-tau drugs for Alzheimer's disease: Systematic review and meta-analysis. J Am Geriatr Soc 2022. Oct 8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36208415 Review. https://agsjournals.onlinelibrary.wiley.com/doi/abs/10.1111/jgs.18025
  86. Jump up to: 86.0 86.1 Koch G, Casula EP, Bonni S et al Precuneus magnetic stimulation for Alzheimer's disease: a randomized, sham-controlled trial. Brain. 2022. Oct 25 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36281767 https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awac285/6701823
  87. Jump up to: 87.0 87.1 Chien CG, Huang LC, Li KY, Yang YH. Cognitive effects of cilostazol in Alzheimer's dementia patients with peripheral arterial occlusive disease: A case-control study. Geriatrics Gerontology International. 2023. Jan 23 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36682741 https://onlinelibrary.wiley.com/doi/abs/10.1111/ggi.14542
  88. Jump up to: 88.0 88.1 Brooks M Oral Tau Inhibitor Continues to Show Promise in Alzheimer's Medscape. July 21, 2023 https://www.medscape.com/viewarticle/994646
  89. Lucey BP, Liu H, Toedebusch CD et al Suvorexant Acutely Decreases Tau Phosphorylation and Abeta in the Human CNS. Ann Neurol. 2023 Jul;94(1):27-40 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36897120 PMCID: PMC10330114 (available on 2024-07-01)
  90. Jump up to: 90.0 90.1 90.2 Lancaster C Uncovering the Unexpected: Developing a Novel Anti-Tau Therapy. The Scientist. Dec 31, 2024 https://www.the-scientist.com/uncovering-the-unexpected-developing-a-novel-anti-tau-therapy-72439
    Hou K, Pan H, Shahpasand-Kroner H et al D-peptide-magnetic nanoparticles fragment tau fibrils and rescue behavioral deficits in a mouse model of Alzheimer's disease. Sci Adv. 2024 May 3;10(18):eadl2991. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38691615 PMCID: PMC11062580 Free PMC article. https://www.science.org/doi/10.1126/sciadv.adl2991
    Hou K, Ge P, Sawaya MR et al How short peptides can disassemble ultra-stable tau fibrils extracted from Alzheimer's disease brain by a strain-relief mechanism. bioRxiv [Preprint]. 2024 Mar 29:2024.03.25.586668. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38585812 Free PMC article. Preprint.