New pharmacological options in the treatment of Alzheimer‘s disease

Authors: L. Kleinová 1,2;  J. Cerman 2;  J. Hlávka 3;  J. Hort 2
Authors‘ workplace: Všeobecné lékařství, 1. LF UK, Praha 1;  Kognitivní centrum, Neurologická klinika 2. LF UK a FN Motol, Praha 2;  Schaeffer Center for Health Policy and Economics, University of Southern California, Los Angeles, USA 3
Published in: Cesk Slov Neurol N 2022; 85(6): 462-469
Category: Review Article


A new era of innovative treatment options for Alzheimer‘s disease is emerging. New goals of treatment are being developed with various monoclonal antibodies targeting potentially pathological molecules involved in the pathogenesis of Alzheimer‘s disease. The aim of this review is to acquaint the reader with new potential drugs, while most of those mentioned in this review are in the third phase of clinical trials.


neuropsychiatric symptoms – tau protein – Alzheimer’s disease – neuroprotection – phase three testing of new drugs – β-amyloid – neuroinflammatory theory


1. World Health Organization. Dementia. [online]. Available from URL: https: //

2. Jarrott B. Tacrine: in vivo veritas. Pharmacol Res 2017; 116: 29–31. doi: 10.1016/j.phrs.2016.12.033.

3. Franková V. Dlouhodobé podávání kognitiv u Alzheimerovy nemoci. Psychiatr Pro Praxi 2004; 9 (4): 201–205.

4. Státní ústav pro kontrolu léčiv. Ebixa product information. [online]. Dostupné z URL: https: //

5. European Medicines Agency. Aduhelm: Withdrawal of the marketing authorisation application. [online]. Dostupné z: https: //

6. Biogen. EMERGE and ENGAGE topline results: two phase 3 studies to evaluate aducanumab in patients with early Alzheimer’s disease. [online]. Available from URL: https: //­

7. Knopman DS, Jones D, Greicius MD. Failure to demonstrate efficacy of aducanumab: an analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019. Alzheimers Dement 2021; 17 (4): 696–701. doi: 10.1002/alz.12213.

8. Alzforum. Therapeutics. [online]. Available from URL: https: // words=#results.

9. Abbott A. Could drugs prevent Alzheimer’s? These trials aim to find out. Nature 2022; 603 (7900): 216–219. doi: 10.1038/d41586-022-00651-0.

10. Salloway S, Chalkias S, Barkhof F et al. Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early Alzheimer disease. JAMA Neurol 2022; 79 (1): 13–21. doi: 10.1001/jamaneurol.2021.4161.

11. Koudelková M. Praktické zkušenosti s laboratorní dia­gnostikou Alzheimerovy nemoci pomocí tau proteinu, fosfo-tau proteinu a beta amyloidu v likvoru. Neurol Pro Praxi 2009; 10 (5): 290–293.

12. Doležalová I, Bolčák K, Kuba R. Využití pozitronové emisní tomografie (PET) v neurologii. Neurol Pro Praxi 2014; 15 (1): 16–21.

13. Alzforum. Networking for a cure. [online]. Dostupné z: https: // fda_statuses%5B%5D=183&target_types=&the­rapy_types=&conditions=&keywords-entry=&keywords= #results.

14. Swanson CJ, Zhang Y, Dhadda S et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer‘s disease with lecanemab, an anti-Aβ protofibril antibody. Alzheimers Res Ther 2021; 13 (1): 80. doi: 10.1186/s13195-021-00813-8.

15. Reuters. Alzheimer‘s drug study yields positive results, say makers Eisai and Biogen. [online]. Dostupné z: https: //

16. Klein G, Delmar P, Kerchner GA et al. Thirty-six-month amyloid positron emission tomography results show continued reduction in amyloid burden with subcutaneous Gantenerumab. J Prev Alzheimers Dis 2021; 8 (1): 3–6. doi: 10.14283/jpad.2020.68.

17. Mintun MA, Lo AC, Duggan Evans C et al. Donanemab in early Alzheimer‘s disease. N Engl J Med 2021; 384 (18): 1691–1704. doi: 10.1056/NEJMoa2100708.

18. Kocis P, Tolar M, Yu J et al. Elucidating the Aβ42 anti-aggregation mechanism of action of tramiprosate in Alzheimer‘s disease: integrating molecular analytical methods, pharmacokinetic and clinical data. CNS Drugs 2017; 31 (6): 495–509. doi: 10.1007/s40263-017-0434-z.

19. Alzheon. Apollo E4: phase 3 study to evaluate efficacy of ALZ-801 in ApoE4/4 early AD subjects. [online]. Available from URL: https: //

20. Abushakra S, Porsteinsson A, Scheltens P et al. Clinical effects of tramiprosate in apoE4/4 homozygous patients with mild Alzheimer’s disease suggest disease modification potential. J Prev Alzheimers Disease 2017; 4 (3): 149–156. doi: 10.14283/jpad.2017.26.

21. Alzheon. Projected readout of Alzheimer’s late-stage trials. ALZ-801 (valiltramiprosate) potentially first oral disease modifying drug. [online]. Available from URL: https: //

22. Státní ústav pro kontrolu léčiv. Pentatop. [online]. Available from URL: https: //

23. AZTherapies. Alzheimer‘s disease. A complex disease needing a multi-modal approach. [online]. Dostupné z: https: //

24. Xiao S, Chan P, Wang T et al. A 36-weekmulticenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer‘s dementia. Alzheimers Res Ther 2021; 13 (1): 62. doi: 10.1186/s13195-021-00795-7.

25. Mediately. Levetiracetam. [online]. Available from URL: https: //

26. Kumar A, Maini K, Kadian R. Levetiracetam. In: Stat Pearls. [online]. Available from URL: https: //

27. Sen A, Akinola M, Tai XY et al. An investigation of Levetiracetam in Alzheimer‘s disease (ILiAD): a double-blind, placebo-controlled, randomised crossover proof of concept study. Trials 2021; 22 (1): 508. doi: 10.1186/s13063-021-05404-4.

28. Willis BA, Sundell K, Lachno DR et al. Central pharmacodynamic aktivity of solanezumab in mild Alzheimer‘s disease dementia. Alzheimers Dement (N Y) 2018; 4: 652–660. doi: 10.1016/j.trci.2018.10.001.

29. 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 (4): 321–330. doi: 10.1056/NEJMoa1705971.

30. Wang CY, Wang PN, Chiu MJ et al. UB-311, a novel UBITh® amyloid β peptide vaccine for mild Alzheimer‘s disease. Alzheimers Dement (N Y) 2017; 3 (2): 262–272. doi: 10.1016/j.trci.2017.03.005.

31. Alzforum. 2021 – a turning point for Alzheimer’s research and therapy? [online]. Available from URL: https: //

32. Ji C, Sigurdsson EM. Current status of clinical trials on Tau immunotherapies. Drugs 2021; 81 (10): 1135–1152. doi: 10.1007/s40265-021-01546-6.

33. 2021 Alzheimer‘s Association International Conference. [online]. Available from URL: https: //

34. CTAD. The journal of prevention of Alzhemiers disease. [online]. Available from URL: https: //

35. AAIC. Alzheimer‘s Association International Conference. [online]. Available from URL: https: //

36. U.S. National Library of Medicine. A Study of JNJ-63733657 in participants with early Alzheimer‘s disease (autonomy). [online]. Available from URL: https: //

37. ADPD 2021. AD/PD 2022 – advances in science and therapy. [online]. Available from URL: https: //

38. U.S. National Library od Medicine. A study to test the efficacy, safety, and tolerability of bepranemab (UCB0107) in patients with mild cognitive impairment or mild Alzheimer‘s disease (AD). [online]. Available from URL: https: //

39. Eisai Global. First subject enrolled in phase II/III study of EISAI’S ANTI-MTBR TAU antibody E2814 for dominantly inherited Alzheimer‘s disease (DIAD), conducted by DIAN-TU. [online]. Available from URL: https: //

40. AC Immune. AC immune’s Alzheimer’s vaccine generates potent anti-pTau antibody response in a phase 1b/2a study. [online]. Available from URL: https: //

41. Novak P, Kovacech B, Katina S et al. ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer’s disease. Nat Aging 2021; 1 (6): 521–534. doi: 10.1038/s43587-021-00070-2.

42. Wilcock GK, Gauthier S, Frisoni GB et al. Potential of low dose leuco-methylthioninium bis (hydro­methanesulphonate) (LMTM) monotherapyfor treatment of mild Alzheimer‘s disease: cohort analysis as modified primary outcome in a phase III clinical trial. J Alzheimers Dis 2018; 61 (1): 435–457. doi: 10.3233/JAD-170560.

43. Státní ústav pro kontrolu léčiv. Pioglitazon. [online]. Dostupné z URL: https: // Bwith_adv%5D=0&data%5Blisting%5D=20&search=Vyhle­dat&page=1.

44. Saunders AM, Burns DK, Gottschalk WK. Reassessment of pioglitazone for Alzheimer‘s disease. Front Neurosci 2021; 15: 666958. doi: 10.3389/fnins.2021.666958.

45. AVANIR Pharmaceuticals. Avanir Pharmaceuticals, Inc. reports data from the second phase 3 study evaluating ivestigational AVP-786 for the treatment of moderate-to-severe agitation in patients with Alzheimer’s dementia. [online]. Available from URL: https: //

46. Mediately. Aripiprazol. [online]. Available from URL: https: //

47. Park SY, Shin HK, Lee WS et al. Neuroprotection by aripiprazoleagainst β-amyloid-induced toxicity by P-CK2α activation via inhibitionof GSK-3β. Oncotarget 2017; 8 (66): 110380–110391. doi: 10.18632/oncotarget.22777.

48. Mediately. Brexpiprazol. [online]. Available from URL: https: //

49. Frampton JE. Brexpiprazole: a review in schizophrenia. Drugs 2019; 79 (2): 189–200. doi: 10.1007/s40265-019-1052-5.

50. Grossberg GT, Kohegyi E, Mergel V et al. Efficacy and safety of brexpiprazole for the treatment of agitation in Alzheimer‘s dementia: two 12-week, randomized, double-blind, placebo-controlled trials. Am J Geriatr Psychiatry 2020; 28 (4): 383–400. doi: 10.1016/j.jagp.2019.09.009.

51. Mediately. Citalopram. [online]. Available from URL: https: //

52. Klaassens BL, van Gerven JMA, Klaassen ES et al. Cholinergic and serotonergic modulation of resting state functional brain connectivity in Alzheimer‘s disease. Neuroimage 2019; 199: 143–152. doi: 10.1016/j.neuroimage.2019.05.044.

53. Mediately. Guanfacin. [online]. Available from URL: https: //

54. Jäkälä P, Riekkinen M, Sirviö J et al. Guanfacine, but not clonidine, improves planning and working memory performance in humans. Neuropsychopharmacology 1999; 20 (5): 460–470. doi: 10.1016/S0893-133X (98) 00127-4.

55. Barcelos NM, Van Ness PH, Wagner AF et al. Guanfacine treatment for prefrontal cognitive dysfunction in older participants: a randomized clinical trial. Neurobio­l Aging 2018; 70: 117–124. doi: 10.1016/j.neurobio­laging.2018.05.033.

56. Cooper D, Gupta V. Lumateperone. Treasure Island (FL): StatPearls Publishing 2022.

57. Cummings J, Ballard C, Tariot P et al. Pimavanserin: potential treatment for dementia-related psychosis. J Prev Alzheimers Dis 2018; 5 (4): 253–258. doi: 10.14283/jpad.2018.29.

58. Gugliandolo A, Chiricosta L, Silvestro S et al. α-tocopherol modulates non-amyloidogenic pathway and autophagy in an in vitro model of Alzheimer‘s disease: a transcriptional study. Brain Sci 2019; 9 (8): 196. doi: 10.3390/brainsci9080196.

59. Mediately. Vitamin E ZENTIVA. [online]. Dostupné z URL: https: // e-zentiva-pil.

60. Li T, Martin E, Abada YS et al. Effects of chronic masitinib treatment in APPswe/PSEN1dE9 transgenic mice modeling Alzheimer‘s disease. J Alzheimers Dis 2020; 76 (4): 1339–1345. doi: 10.3233/JAD-200466.

61. Mediately. Semaglutid. [online]. Available from URL: https: //

62. Chang YF, Zhang D, Hu WM et al. Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apotosis. J Clin Neurosci 2020; 81: 234–239. doi: 10.1016/j.jocn.2020.09.054.

63. Avgerinos KI, Ferrucci L, Kapogiannis D. Effects of monoclonal antibodies against amyloid-β on clinical and bio­marker outcomes and adverse event risks: a systematic review and meta-analysis of phase III RCTs in Alzheimer‘s disease. Ageing Res Rev 2021; 68: 101339. doi: 10.1016/j.arr.2021.101339.

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