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Journal of Neurorestoratology 2015, 3(1): 1-9 https://doi.org/10.2147/JN.S74143
Review | Open Access | Issue | Published: 15 December 2014

Clinical neurorestorative progress in Alzheimer’s disease

Show Author's Information Liyan Qiao1( ),  Hongyun Huang2,3,  Dafin F Muresanu4,5
Department of Neurology, Tsinghua University Yuquan Hospital,
Beijing Rehabilitation Hospital of Capital Medical University,
Beijing Hongtianji Neuroscience Academy, Beijing, People’s Republic of China
Department of Clinical Neurosciences, Iuliu Haţieganu University of Medicine and Pharmacy,
RoNeuro Institute for Neurological Research and Diagnosis, Cluj-Napoca, Romania
Keywords:
Alzheimer’s disease, cell therapy, neurorastorlogy, medicine
Cite this article:
Qiao L, Huang H, Muresanu DF. Clinical neurorestorative progress in Alzheimer’s disease. Journal of Neurorestoratology, 2015, 3(1): 1-9. https://doi.org/10.2147/JN.S74143
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Abstract Full text About this article

Alzheimer’s disease (AD) is the most prevalent type of dementia, and its neuropathology is characterized by the deposition of insoluble β-amyloid peptides and intracellular neurofibrillary tangles and the loss of diverse neurons. Although much is known about the neurobiology of AD, few treatments are available to arrest or slow the illness. There is an urgent need for novel therapeutic approaches for AD. We reviewed the recent improvements in the neurorastorlogy strategies for AD, including medicine, bioengineering and neuromodulation and clinical cell therapy. We emphasized that cell therapy may be an promising treatment for AD.


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About this article

Clinical neurorestorative progress in Alzheimer’s disease

Show Author's information Liyan Qiao1( ), Hongyun Huang2,3, Dafin F Muresanu4,5
Department of Neurology, Tsinghua University Yuquan Hospital,
Beijing Rehabilitation Hospital of Capital Medical University,
Beijing Hongtianji Neuroscience Academy, Beijing, People’s Republic of China
Department of Clinical Neurosciences, Iuliu Haţieganu University of Medicine and Pharmacy,
RoNeuro Institute for Neurological Research and Diagnosis, Cluj-Napoca, Romania

Abstract

Alzheimer’s disease (AD) is the most prevalent type of dementia, and its neuropathology is characterized by the deposition of insoluble β-amyloid peptides and intracellular neurofibrillary tangles and the loss of diverse neurons. Although much is known about the neurobiology of AD, few treatments are available to arrest or slow the illness. There is an urgent need for novel therapeutic approaches for AD. We reviewed the recent improvements in the neurorastorlogy strategies for AD, including medicine, bioengineering and neuromodulation and clinical cell therapy. We emphasized that cell therapy may be an promising treatment for AD.

Keywords: Alzheimer’s disease, cell therapy, neurorastorlogy, medicine

References(86)

1.
Victor M, Ropper AH. Degenerative diseases of the nervous system. In: Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology. 1106–1174.
Google Scholar
2.
Alzheimer’s Association. 2014 Alzheimer’s disease facts and figures. Alzheimers Dement. 2014;10(2):e47–e92.
DOI Google Scholar
3.
Drachman DA. The amyloid hypothesis, time to move on: Amyloid is the downstream result, not cause, of Alzheimer’s disease. Alzheimers Dement. 2014;10(3):372–380.
DOI Google Scholar
4.
Hyman BT, Phelps CH, Beach TG, et al. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement. 2012;8(1):1–13.
DOI Google Scholar
5.
Nelson PT, Alafuzoff I, Bigio EH, et al. Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol. 2012;71(5):362–381.
DOI Google Scholar
6.
Parsons CG, Danysz W, Dekundy A, Pulte I. Memantine and cholinesterase inhibitors: complementary mechanisms in the treatment of Alzheimer’s disease. Neurotox Res. 2013;24(3):358–369.
DOI Google Scholar
7.
Muoio V, Persson PB, Sendeski MM. The neurovascular unit – concept review. Acta Physiol (Oxf). 2014;210(4):790–798.
DOI Google Scholar
8.
Bell RD, Zlokovic BV. Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer’s disease. Acta Neuropathol. 2009; 118(1):103–113.
DOI Google Scholar
9.
Baloyannis SJ, Baloyannis IS. The vascular factor in Alzheimer’s disease: a study in Golgi technique and electron microscopy. J Neurol Sci. 2012;322(1–2):117–121.
DOI Google Scholar
10.
Panza F, Frisardi V, Solfrizzi V, et al. Interacting with γ-secretase for treating Alzheimer’s disease: from inhibition to modulation. Curr Med Chem. 2011;18(35):5430–5447.
DOI Google Scholar
11.
Crump CJ, Johnson DS, Li YM. Development and mechanism of γ-secretase modulators for Alzheimer’s disease. Biochemistry. 2013;52(19):3197–3216.
DOI Google Scholar
12.
Doody RS, Raman R, Farlow M, et al; Alzheimer’s Disease Cooperative Study Steering Committee; Semagacestat Study Group. A phase 3 trial of semagacestat for treatment of Alzheimer’s disease. N Engl J Med. 2013;369(4):341–350.
DOI Google Scholar
13.
Imbimbo BP, Giardina GA. γ-secretase inhibitors and modulators for the treatment of Alzheimer’s disease: disappointments and hopes. Curr Top Med Chem. 2011;11(12):1555–1570.
DOI Google Scholar
14.
Green RC, Schneider LS, Amato DA, et al; Tarenflurbil Phase 3 Study Group. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial. JAMA. 2009;302(23):2557–2564.
DOI Google Scholar
15.
Wisniewski T, Goñi F. Immunotherapy for Alzheimer’s disease. Biochem Pharmacol. 2014;88(4):499–507.
DOI Google Scholar
16.
Lambracht-Washington D, Rosenberg RN. Anti-amyloid beta to tau – based immunization: Developments in immunotherapy for Alzheimer disease. Immunotargets Ther. 2013;2013(2):105–114.
DOI Google Scholar
17.
Lambracht-Washington D, Rosenberg RN. Advances in the development of vaccines for Alzheimer’s disease. Discov Med. 2013;15(84):319–326.
Google Scholar
18.
Honig LS. Translational research in neurology: dementia. Arch Neurol. 2012;69(8):969–977.
DOI Google Scholar
19.
Loeffler DA. Intravenous immunoglobulin and Alzheimer’s disease: what now? J Neuroinflammation. 2013;10(1):70.
DOI Google Scholar
20.
Townsend KP, Praticò D. Novel therapeutic opportunities for Alzheimer’s disease: focus on nonsteroidal anti-inflammatory drugs. FASEB J. 2005;19(12):1592–1601.
DOI Google Scholar
21.
ADAPT-FS Research Group. Follow-up evaluation of cognitive function in the randomized Alzheimer’s Disease Anti-inflammatory Prevention Trial and its Follow-up Study. Alzheimers Dement. Epub July 8, 2014.
Google Scholar
22.
Rockenstein E, Torrance M, Mante M, et al. Cerebrolysin decreases amyloid-beta production by regulating amyloid protein precursor maturation in a transgenic model of Alzheimer’s disease. J Neurosci Res. 2006;83(7):1252–1261.
DOI Google Scholar
23.
Ubhi K, Rockenstein E, Doppler E, et al. Neurofibrillary and neurodegenerative pathology in APP-transgenic mice injected with AAV2-mutant TAU: neuroprotective effects of Cerebrolysin. Acta Neuropathol. 2009;117(6):699–712.
DOI Google Scholar
24.
Ruether E, Husmann R, Kinzler E, et al. A 28-week, double-blind, placebo-controlled study with Cerebrolysin in patients with mild to moderate Alzheimer’s disease. Int Clin Psychopharmacol. 2001;16(5):253–263.
DOI Google Scholar
25.
Panisset M, Gauthier S, Moessler H, Windisch M; Cerebrolysin Study Group. Cerebrolysin in Alzheimer’s disease: a randomized, double-blind, placebo-controlled trial with a neurotrophic agent. J Neural Transm. 2002;109(7–8):1089–1104.
DOI Google Scholar
26.
Muresanu DF, Rainer M, Moessler H. Improved global function and activities of daily living in patients with AD: a placebo-controlled clinical study with the neurotrophic agent Cerebrolysin. J Neural Transm Suppl. 2002;(62):277–285.
DOI Google Scholar
27.
Alvarez XA, Cacabelos R, Laredo M, et al. A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer’s disease. Eur J Neurol. 2006;13(1):43–54.
DOI Google Scholar
28.
Alvarez XA, Sampedro C, Cacabelos R, et al. Reduced TNF-α and increased IGF-I levels in the serum of Alzheimer’s disease patients treated with the neurotrophic agent cerebrolysin. Int J Neuropsychopharmacol. 2009;12(7):867–872.
DOI Google Scholar
29.
Álvarez XA, Fuentes P. Cerebrolysin in Alzheimer’s Disease. Drugs Today (Barc). 2011;47(7):487–513.
DOI Google Scholar
30.
Plosker GL, Gauthier S. Cerebrolysin: a review of its use in dementia. Drugs Aging. 2009;26(11):893–915.
DOI Google Scholar
31.
Álvarez XA, Fuentes P. Cerebrolysin in Alzheimer’s disease. Drugs Today (Barc). 2011;47(7):487–513.
DOI Google Scholar
32.
Allegri RF, Guekht A. Cerebrolysin improves symptoms and delays progression in patients with Alzheimer’s disease and vascular dementia. Drugs Today (Barc). 2012;48 Suppl A:S25–S41.
Google Scholar
33.
Iadecola C. The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathol. 2010;120(3):287–296.
DOI Google Scholar
34.
Muresanu DF, Popa-Wagner A, Stan A, Buga AM, Popescu BO. The vascular component of Alzheimer’s disease. Curr Neurovasc Res. 2014;11(2):168–176.
DOI Google Scholar
35.
Chen N, Yang M, Guo J, Zhou M, Zhu C, He L. Cerebrolysin for vascular dementia. Cochrane Database Syst Rev. 2013;1:CD008900.
DOI Google Scholar
36.
Blurton-Jones M, Spencer B, Michael S, et al. Neural stem cells genetically-modified to express neprilysin reduce pathology in Alzheimer transgenic models. Stem Cell Res Ther. 2014;5(2):46.
DOI Google Scholar
37.
Park D, Lee HJ, Joo SS, et al. Human neural stem cells over-expressing choline acetyltransferase restore cognition in rat model of cognitive dysfunction. Exp Neurol. 2012;234(2):521–526.
DOI Google Scholar
38.
Lee HJ, Lim IJ, Park SW, Kim YB, Ko Y, Kim SU. Human neural stem cells genetically modified to express human nerve growth factor (NGF) gene restore cognition in the mouse with ibotenic acid-induced cognitive dysfunction. Cell Transplant. 2012;21(11):2487–2496.
DOI Google Scholar
39.
Wu L, Sluiter AA, Guo HF, et al. Neural stem cells improve neuronal survival in cultured postmortem brain tissue from aged and Alzheimer patients. J Cell Mol Med. 2008;12(5A):1611–1621.
DOI Google Scholar
40.
Cenciarelli C, Budoni M, Mercanti D, et al. In vitro analysis of mouse neural stem cells genetically modified to stably express human NGF by a novel multigenic viral expression system. Neurol Res. 2006;28(5):505–512.
DOI Google Scholar
41.
Marei HE, Farag A, Althani A, et al. Human olfactory bulb neural stem cells expressing hNGF restore cognitive deficit in Alzheimer’s disease rat model. J Cell Physiol. 2015;230(1):116–130.
DOI Google Scholar
42.
Li LY, Li JT, Wu QY, et al. Transplantation of NGF-gene-modified bone marrow stromal cells into a rat model of Alzheimer’ disease. J Mol Neurosci. 2008;34(2):157–163.
DOI Google Scholar
43.
Liang J, Wu S, Zhao H, et al. Human umbilical cord mesenchymal stem cells derived from Wharton’s jelly differentiate into cholinergic-like neurons in vitro. Neurosci Lett. 2013;532:59–63.
DOI Google Scholar
44.
Tuszynski MH, Thal L, Pay M, et al. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med. 2005;11(5):551–555.
DOI Google Scholar
45.
Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov. 2011; 10(3):209–219.
DOI Google Scholar
46.
Ziabreva I, Perry E, Perry R, et al. Altered neurogenesis in Alzheimer’s disease. J Psychosom Res. 2006;61(3):311–316.
DOI Google Scholar
47.
Sanchez-Ramos J, Cimino C, Avila R, et al. Pilot study of granulocyte-colony stimulating factor for treatment of Alzheimer’s disease. J Alzheimers Dis. 2012;31(4):843–855.
DOI Google Scholar
48.
Laske C, Stellos K, Stransky E, et al. Decreased plasma and cerebrospinal fluid levels of stem cell factor in patients with early Alzheimer’s disease. J Alzheimers Dis. 2008;15(3):451–460.
DOI Google Scholar
49.
Lovell MA, Geiger H, Van Zant GE, Lynn BC, Markesbery WR. Isolation of neural precursor cells from Alzheimer’s disease and aged control postmortem brain. Neurobiol Aging. 2006;27(7):909–917.
DOI Google Scholar
50.
Seo SW, Lee JII, Kim CH, et al. A phase I trial of parenchymal injection of umbilical cord stem cells in Alzheimer’s disease. Alzheimers Dement. 2013;9(Suppl 4):S291.
DOI Google Scholar
51.
Laxton AW, Tang-Wai DF, McAndrews MP, et al. A phase I trial of deep brain stimulation of memory circuits in Alzheimer’s disease. Ann Neurol. 2010;68(4):521–534.
DOI Google Scholar
52.
Fontaine D, Deudon A, Lemaire JJ, et al. Symptomatic treatment of memory decline in Alzheimer’s disease by deep brain stimulation: a feasibility study. J Alzheimers Dis. 2013;34(1):315–323.
DOI Google Scholar
53.
Lefaucheur JP, André-Obadia N, Antal A, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. Epub June 5, 2014.
Google Scholar
54.
Rabey JM, Dobronevsky E, Aichenbaum S, Gonen O, Marton RG, Khaigrekht M. Repetitive transcranial magnetic stimulation combined with cognitive training is a safe and effective modality for the treatment of Alzheimer’s disease: a randomized, double-blind study. J Neural Transm. 2013;120(5):813–819.
DOI Google Scholar
55.
Eliasova I, Anderkova L, Marecek R, Rektorova I. Non-invasive brain stimulation of the right inferior frontal gyrus may improve attention in early Alzheimer’s disease: A pilot study. J Neurol Sci. Epub August 29, 2014.
Google Scholar
56.
Demars M, Hu YS, Gadadhar A, Lazarov O. Impaired neurogenesis is an early event in the etiology of familial Alzheimer’s disease in transgenic mice. J Neurosci Res. 2010;88(10):2103–2117.
DOI Google Scholar
57.
Rodríguez JJ, Jones VC, Verkhratsky A. Impaired cell proliferation in the subventricular zone in an Alzheimer’s disease model. Neuroreport. 2009;20(10):907–912.
DOI Google Scholar
58.
Haughey NJ, Nath A, Chan SL, Borchard AC, Rao MS, Mattson MP. Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer’s disease. J Neurochem. 2002;83(6):1509–1524.
DOI Google Scholar
59.
Hayashi Y, Kashiwagi K, Ohta J, Nakajima M, Kawashima T, Yoshikawa K. Alzheimer amyloid protein precursor enhances proliferation of neural stem cells from fetal rat brain. Biochem Biophys Res Commun. 1994;205(1):936–943.
DOI Google Scholar
60.
Wen PH, Shao X, Shao Z, et al. Overexpression of wild type but not an FAD mutant presenilin-1 promotes neurogenesis in the hippocampus of adult mice. Neurobiol Dis. 2002;10(1):8–19.
DOI Google Scholar
61.
Chevallier NL, Soriano S, Kang DE, Masliah E, Hu G, Koo EH. Perturbed neurogenesis in the adult hippocampus associated with presenilin-1 A246E mutation. Am J Pathol. 2005;167(1):151–159.
DOI Google Scholar
62.
Zhang X, Jin G, Tian M, Qin J, Huang Z. The denervated hippocampus provides proper microenvironment for the survival and differentiation of neural progenitors. Neurosci Lett. 2007;414(2):115–120.
DOI Google Scholar
63.
Oh SH, Kim HN, Park HJ, Shin JY, Lee PH. Mesenchymal stem cells increase hippocampal neurogenesis and neuronal differentiation by enhancing the Wnt signaling pathway in Alzheimer’s disease model. Cell Transplant. March 7, 2014.
Google Scholar
64.
Zilka N, Zilkova M, Kazmerova Z, Sarissky M, Cigankova V, Novak M. Mesenchymal stem cells rescue the Alzheimer’s disease cell model from cell death induced by misfolded truncated tau. Neuroscience. 2011;193:330–337.
DOI Google Scholar
65.
Shin JY, Park HJ, Kim HN, et al. Mesenchymal stem cells enhance autophagy and increase β-amyloid clearance in Alzheimer disease models. Autophagy. 2014;10(1):32–44.
DOI Google Scholar
66.
Zilka N, Zilkova M, Kazmerova Z, Sarissky M, Cigankova V, Novak M. Mesenchymal stem cells rescue the Alzheimer’s disease cell model from cell death induced by misfolded truncated tau. Neuroscience. 2011;193:330–337.
DOI Google Scholar
67.
Lee JK, Jin HK, Bae JS. Bone marrow-derived mesenchymal stem cells attenuate amyloid β-induced memory impairment and apoptosis by inhibiting neuronal cell death. Curr Alzheimer Res. 2010;7(6):540–548.
DOI Google Scholar
68.
Lee JK, Jin HK, Bae JS. Bone marrow-derived mesenchymal stem cells reduce brain amyloid-beta deposition and accelerate the activation of microglia in an acutely induced Alzheimer’s disease mouse model. Neurosci Lett. 2009;450(2):136–141.
DOI Google Scholar
69.
Bae JS, Jin HK, Lee JK, Richardson JC, Carter JE. Bone marrow-derived mesenchymal stem cells contribute to the reduction of amyloid-β deposits and the improvement of synaptic transmission in a mouse model of pre-dementia Alzheimer’s disease. Curr Alzheimer Res. 2013;10(5):524–531.
DOI Google Scholar
70.
Park D, Yang G, Bae DK, et al. Human adipose tissue-derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice. J Neurosci Res. 2013;91(5):660–670.
DOI Google Scholar
71.
Kim S, Chang KA, Kim Ja, et al. The preventive and therapeutic effects of intravenous human adipose-derived stem cells in Alzheimer’s disease mice. PLoS One. 2012;7(9):e45757.
DOI Google Scholar
72.
Xuan AG, Luo M, Ji WD, Long DH. Effects of engrafted neural stem cells in Alzheimer’s disease rats. Neurosci Lett. 2009;450(2):167–171.
DOI Google Scholar
73.
Moghadam FH, Alaie H, Karbalaie K, Tanhaei S, Nasr Esfahani MH, Baharvand H. Transplantation of primed or unprimed mouse embryonic stem cell-derived neural precursor cells improves cognitive function in Alzheimerian rats. Differentiation. 2009;78(2–3):59–68.
DOI Google Scholar
74.
Fujiwara N, Shimizu J, Takai K, et al. Restoration of spatial memory dysfunction of human APP transgenic mice by transplantation of neuronal precursors derived from human iPS cells. Neurosci Lett. 2013;557 Pt B:129–134.
DOI Google Scholar
75.
Ooi L, Sidhu K, Poljak A, et al. Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer’s disease. J Neural Transm. 2013;120(1):103–111.
DOI Google Scholar
76.
Yagi T, Ito D, Okada Y, et al. Modeling familial Alzheimer’s disease with induced pluripotent stem cells. Hum Mol Genet. 2011;20(23):4530–4539.
DOI Google Scholar
77.
Lovell MA, Geiger H, Van Zant GE, Lynn BC, Markesbery WR. Isolation of neural precursor cells from Alzheimer’s disease and aged control postmortem brain. Neurobiol Aging. 2006;27(7):909–917.
DOI Google Scholar
78.
Choi SS, Lee SR, Kim SU, Lee HJ. Alzheimer’s disease and stem cell therapy. Exp Neurobiol. 2014;23(1):45–52.
DOI Google Scholar
79.
Chang KA, Kim JA, Kim S, Jet al. Therapeutic potentials of neural stem cells treated with fluoxetine in Alzheimer’s disease. Neurochem Int. 2012;61(6):885–891.
DOI Google Scholar
80.
Chadwick W, Mitchell N, Caroll J, et al. Amitriptyline-mediated cognitive enhancement in aged 3× Tg Alzheimer’s disease mice is associated with neurogenesis and neurotrophic activity. PLoS One. 2011;6(6):e21660.
DOI Google Scholar
81.
Ridwan S, Bauer H, Frauenknecht K, Hefti K, von Pein H, Sommer CJ. Distribution of the hematopoietic growth factor G-CSF and its receptor in the adult human brain with specific reference to Alzheimer’s disease. J Anat. 2014;224(4):377–391.
DOI Google Scholar
82.
Prakash A, Medhi B, Chopra K. Granulocyte colony stimulating factor (GCSF) improves memory and neurobehavior in an amyloid-β induced experimental model of Alzheimer’s disease. Pharmacol Biochem Behav. 2013;110:46–57.
DOI Google Scholar
83.
Tsai KJ, Tsai YC, Shen CK. G-CSF rescues the memory impairment of animal models of Alzheimer’s disease. J Exp Med. 2007;204(6):1273–1280.
DOI Google Scholar
84.
Sanchez-Ramos J, Song S, Sava V, et al. Granulocyte colony stimulating factor decreases brain amyloid burden and reverses cognitive impairment in Alzheimer’s mice. Neuroscience. 2009;163(1):55–72.
DOI Google Scholar
85.
Shin JW, Lee JK, Lee JE, et al. Combined effects of hematopoietic progenitor cell mobilization from bone marrow by granulocyte colony stimulating factor and AMD3100 and chemotaxis into the brain using stromal cell-derived factor-1α in an Alzheimer’s disease mouse model. Stem Cells. 2011;29(7):1075–1089.
DOI Google Scholar
86.
Parthsarathy V, Hölscher C. Chronic treatment with the GLP1 analogue liraglutide increases cell proliferation and differentiation into neurons in an AD mouse model. PLoS One. 2013;8(3):e58784.
DOI Google Scholar
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Published: 15 December 2014
Issue date: December 2015

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