3,247
Views
424
CrossRef citations to date
0
Altmetric
Review

Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics

, , , &
Pages 5541-5554 | Published online: 19 Jul 2019

References

  • Adav SS, Sze SK. Insight of brain degenerative protein modifications in the pathology of neurodegeneration and dementia by proteomic profiling. Mol Brain. 2016;9(1):92. doi:10.1186/s13041-016-0272-927809929
  • Leandro P, Gomes CM. Protein misfolding in conformational disorders: rescue of folding defects and chemical chaperoning. Mini Rev Med Chem. 2008;8(9):901–911.18691147
  • Tran L, Ha-Duong T. Exploring the Alzheimer amyloid-β peptide conformational ensemble: A review of molecular dynamics approaches. Peptides. 2015;69:86–91. doi:10.1016/j.peptides.2015.04.00925908410
  • Horwich A. Protein aggregation in disease: a role for folding intermediates forming specific multimeric interactions. J Clin Invest. 2002;110(9):1221–1232. doi:10.1172/JCI1678112417558
  • Selkoe DJ. Cell biology of protein misfolding: the examples of Alzheimer‘s and Parkinson‘s diseases. Nat Cell Biol. 2004;6(11):1054. doi:10.1038/ncb1104-105415516999
  • Blessed G, Tomlinson BE, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry. 1968;114(512):797–811.5662937
  • O‘Brien RJ, Wong PC. Amyloid precursor protein processing and Alzheimer‘s disease. Annu Rev Neurosci. 2011;34:185–204. doi:10.1146/annurev-neuro-061010-11361321456963
  • Henry W, Querfurth H, LaFerla F. Mechanisms of disease Alzheimer’s disease. New Engl J Med. 2010;362:329–344. doi:10.1056/NEJMra090914220107219
  • Alzheimer’s A. 2015 Alzheimer‘s disease facts and figures. Alzheimer‘S Dementia. 2015;11(3):332. doi:10.1016/j.jalz.2015.02.003
  • Goedert M. Alzheimer’s and Parkinson’s diseases: the prion concept in relation to assembled Aβ, tau, and α-synuclein. Science. 2015;349(6248):1255555. doi:10.1126/science.125555526250687
  • Chen JX, Yan SS. Role of mitochondrial amyloid-β in Alzheimer‘s disease. J Alzheimer‘S Dis. 2010;20(s2):S569–S578. doi:10.3233/JAD-2010-10035720463403
  • Crews L, Masliah E. Molecular mechanisms of neurodegeneration in Alzheimer‘s disease. Hum Mol Genet. 2010;19(R1):R12–R20. doi:10.1093/hmg/ddq16020413653
  • Oh ES, Savonenko AV, King JF, et al. Amyloid precursor protein increases cortical neuron size in transgenic mice. Neurobiol Aging. 2009;30(8):1238–1244. doi:10.1016/j.neurobiolaging.2007.12.02418304698
  • Thinakaran G, Koo EH. Amyloid precursor protein trafficking, processing, and function. J Biol Chem. 2008;283(44):29615–29619. doi:10.1074/jbc.R80001920018650430
  • Young-Pearse TL, Bai J, Chang R, Zheng JB, LoTurco JJ, Selkoe DJ. A critical function for β-amyloid precursor protein in neuronal migration revealed by in utero RNA interference. J Neurosci. 2007;27(52):14459–14469. doi:10.1523/JNEUROSCI.4701-07.200718160654
  • Meziane H, Dodart J-C, Mathis C, et al. Memory-enhancing effects of secreted forms of the β-amyloid precursor protein in normal and amnestic mice. Proc Natl Acad Sci. 1998;95(21):12683–12688. doi:10.1073/pnas.95.21.126839770546
  • Selkoe DJ. Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer‘s disease. Annu Rev Cell Biol. 1994;10(1):373–403. doi:10.1146/annurev.cb.10.110194.0021057888181
  • Hefter D, Kaiser M, Weyer SW, et al. Amyloid precursor protein protects neuronal network function after hypoxia via control of voltage-gated calcium channels. J Neurosci. 2016;36(32):8356–8371. doi:10.1523/JNEUROSCI.4130-15.201627511009
  • Shoji M, Golde TE, Ghiso J, et al. Production of the Alzheimer amyloid beta protein by normal proteolytic processing. Science. 1992;258(5079):126–129.1439760
  • Kimberly WT, Zheng JB, Guenette S, Selkoe DJ. The intracellular domain of the ß-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner. J Biol Chem. 2001. doi:10.1074/jbc.C100447200
  • Bergmans BA, De Strooper B. γ-secretases: from cell biology to therapeutic strategies. Lancet Neurol. 2010;9(2):215–226. doi:10.1016/S1474-4422(09)70332-120129170
  • Tu S, Okamoto S-I, Lipton SA, Xu H. Oligomeric Aβ-induced synaptic dysfunction in Alzheimer’s disease. Mol Neurodegener. 2014;9(1):48. doi:10.1186/1750-1326-9-4825394486
  • Eftekharzadeh B, Daigle JG, Kapinos LE, et al. Tau protein disrupts nucleocytoplasmic transport in Alzheimer’s disease. Neuron. 2018;99(5):925–940.e927. doi:10.1016/j.neuron.2018.07.03930189209
  • Claeysen S, Cochet M, Donneger R, Dumuis A, Bockaert J, Giannoni P. Alzheimer culprits: cellular crossroads and interplay. Cell Signal. 2012;24(9):1831–1840. doi:10.1016/j.cellsig.2012.05.00822627093
  • Marcus JN, Schachter J. Targeting post-translational modifications on tau as a therapeutic strategy for Alzheimer‘s disease. J Neurogenet. 2011;25(4):127–133. doi:10.3109/01677063.2011.62647122091726
  • Lee VM, Goedert M, Trojanowski JQ. Neurodegenerative tauopathies. Annu Rev Neurosci. 2001;24(1):1121–1159. doi:10.1146/annurev.neuro.24.1.112111520930
  • De Strooper B, Woodgett J. Alzheimer‘s disease: mental plaque removal. Nature. 2003;423(6938):392. doi:10.1038/423392a12761533
  • Phiel CJ, Wilson CA, Lee VM-Y, Klein PS. GSK-3α regulates production of Alzheimer‘s disease amyloid-β peptides. Nature. 2003;423(6938):435. doi:10.1038/nature0164012761548
  • Hernández F, Avila J. The role of glycogen synthase kinase 3 in the early stages of Alzheimers’ disease. FEBS Lett. 2008;582(28):3848–3854. doi:10.1016/j.febslet.2008.10.02618955053
  • Cho J-H, Johnson GV. Glycogen synthase kinase 3β induces caspase-cleaved tau aggregation in situ. J Biol Chem. 2004;279(52):54716–54723. doi:10.1074/jbc.M40336420015494420
  • Kuruva CS, Reddy PH. Amyloid beta modulators and neuroprotection in Alzheimer‘s disease: a critical appraisal. Drug Discov Today. 2017;22(2):223–233. doi:10.1016/j.drudis.2016.10.01027794478
  • Bossy-Wetzel E, Schwarzenbacher R, Lipton SA. Molecular pathways to neurodegeneration. Nat Med. 2004;10(7):S2. doi:10.1038/nm106715272266
  • Nizzari M, Thellung S, Corsaro A, et al. Neurodegeneration in Alzheimer disease: role of amyloid precursor protein and presenilin 1 intracellular signaling. J Toxicol. 2012;2012:187297.
  • Dries DR, Yu G. Assembly, maturation, and trafficking of the γ-secretase complex in Alzheimer‘s disease. Curr Alzheimer Res. 2008;5(2):132–146.18393798
  • Edbauer D, Winkler E, Regula JT, Pesold B, Steiner H, Haass C. Reconstitution of γ-secretase activity. Nat Cell Biol. 2003;5(5):486. doi:10.1038/ncb96012679784
  • Shen J, Kelleher RJ. The presenilin hypothesis of Alzheimer‘s disease: evidence for a loss-of-function pathogenic mechanism. Proc Natl Acad Sci. 2007;104(2):403–409. doi:10.1073/pnas.060833210417197420
  • Waddington CH. The epigenotype. Int J Epidemiol. 2011;41(1):10–13. doi:10.1093/ije/dyr18422186258
  • Lardenoije R, Iatrou A, Kenis G, et al. The epigenetics of aging and neurodegeneration. Prog Neurobiol. 2015;131:21–64. doi:10.1016/j.pneurobio.2015.05.00226072273
  • Sweatt JD. The emerging field of neuroepigenetics. Neuron. 2013;80(3):624–632. doi:10.1016/j.neuron.2013.10.02324183015
  • Tsankova N, Renthal W, Kumar A, Nestler EJ. Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci. 2007;8(5):355. doi:10.1038/nrn213217453016
  • Day JJ, Sweatt JD. DNA methylation and memory formation. Nat Neurosci. 2010;13(11):1319. doi:10.1038/nn.251120975755
  • Landgrave-Gómez J, Mercado-Gómez O, Guevara-Guzmán R. Epigenetic mechanisms in neurological and neurodegenerative diseases. Front Cell Neurosci. 2015;9:58.25774124
  • Sezgin Z, Dincer Y. Alzheimer‘s disease and epigenetic diet. Neurochem Int. 2014;78:105–116. doi:10.1016/j.neuint.2014.09.01225290336
  • Balazs R. Epigenetic mechanisms in Alzheimer‘s disease. Degener Neurol Neuromuscul Dis. 2014;4:85–102. doi:10.2147/DNND.S37341
  • Hernandez DG, Nalls MA, Gibbs JR, et al. Distinct DNA methylation changes highly correlated with chronological age in the human brain. Hum Mol Genet. 2011;20(6):1164–1172. doi:10.1093/hmg/ddq56121216877
  • Mastroeni D, Grover A, Delvaux E, Whiteside C, Coleman PD, Rogers J. Epigenetic mechanisms in Alzheimer‘s disease. Neurobiol Aging. 2011;32(7):1161–1180. doi:10.1016/j.neurobiolaging.2010.08.01721482442
  • Francis YI, Fà M, Ashraf H, et al. Dysregulation of histone acetylation in the APP/PS1 mouse model of Alzheimer‘s disease. J Alzheimer‘S Dis. 2009;18(1):131–139. doi:10.3233/JAD-2009-113419625751
  • Delgado-Morales R, Agís-Balboa RC, Esteller M, Berdasco M. Epigenetic mechanisms during ageing and neurogenesis as novel therapeutic avenues in human brain disorders. Clin Epigenetics. 2017;9(1):67. doi:10.1186/s13148-017-0365-z28670349
  • Ji K, Akgul G, Wollmuth LP, Tsirka SE, Dunaevsky A. Microglia actively regulate the number of functional synapses. PLoS One. 2013;8(2):e56293. doi:10.1371/journal.pone.005629323393609
  • Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer‘s disease. Lancet Neurol. 2015;14(4):388–405. doi:10.1016/S1474-4422(15)70016-525792098
  • Bamberger ME, Harris ME, McDonald DR, Husemann J, Landreth GE. A cell surface receptor complex for fibrillar β-amyloid mediates microglial activation. J Neurosci. 2003;23(7):2665–2674.12684452
  • Liu Y, Walter S, Stagi M, et al. LPS receptor (CD14): a receptor for phagocytosis of Alzheimer‘s amyloid peptide. Brain. 2005;128(8):1778–1789. doi:10.1093/brain/awh53115857927
  • Malito E, Hulse RE, Tang W-J. Amyloid β-degrading cryptidases: insulin degrading enzyme, presequence peptidase, and neprilysin. Cel Mol Life Sci. 2008;65(16):2574–2585. doi:10.1007/s00018-008-8112-4
  • Hickman SE, Allison EK, El Khoury J. Microglial dysfunction and defective β-amyloid clearance pathways in aging Alzheimer‘s disease mice. J Neurosci. 2008;28(33):8354–8360. doi:10.1523/JNEUROSCI.0616-08.200818701698
  • Neumann H, Daly MJ. Variant TREM2 as risk factor for Alzheimer's disease. N Engl J Med. 2013;368(2):182–184. doi:10.1056/NEJMe121315723151315
  • Wang Y, Cella M, Mallinson K, et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model. Cell. 2015;160(6):1061–1071. doi:10.1016/j.cell.2015.01.04925728668
  • Hsieh CL, Koike M, Spusta SC, et al. A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia. J Neurochem. 2009;109(4):1144–1156. doi:10.1111/j.1471-4159.2009.06042.x19302484
  • Valcour VG, Shikuma CM, Watters MR, Sacktor NC. Cognitive impairment in older HIV-1-seropositive individuals: prevalence and potential mechanisms. Aids. 2004;18(Suppl 1):S79. doi:10.1097/00002030-200401001-0001215075502
  • Becker JT, Lopez OL, Dew MA, Aizenstein HJ. Prevalence of cognitive disorders differs as a function of age in HIV virus infection. Aids. 2004;18:11–18. doi:10.1097/00002030-200401001-00003
  • Esiri MM, Biddolph SC, Morris CS. Prevalence of Alzheimer plaques in AIDS. J Neurol, Neurosurg Psychiatry. 1998;65(1):29–33. doi:10.1136/jnnp.65.1.299667557
  • Green DA, Masliah E, Vinters HV, Beizai P, Moore DJ, Achim CL. Brain deposition of beta-amyloid is a common pathologic feature in HIV positive patients. Aids. 2005;19(4):407–411.15750394
  • Pulliam L. HIV regulation of amyloid beta production. J Neuroimmune Pharmacol. 2009;4(2):213–217. doi:10.1007/s11481-009-9151-919288202
  • Scannevin RH. Therapeutic strategies for targeting neurodegenerative protein misfolding disorders. Curr Opin Chem Biol. 2018;44:66–74. doi:10.1016/j.cbpa.2018.05.01829902695
  • Cummings J, Lee G, Mortsdorf T, Ritter A, Zhong K. Alzheimer‘s disease drug development pipeline: 2017. Alzheimer‘S Dementia. 2017;3(3):367–384.
  • Simmons D, Yang T, Massa S, Longo F. Neuroprotective strategies for Alzheimer’s disease prevention and therapy In: Wolfe MS, editor. Developing Therapeutics for Alzheimer‘s Disease. Amsterdam: Elsevier; 2016:437–458.
  • Wadghiri YZ, Sigurdsson EM, Sadowski M, et al. Detection of Alzheimer‘s amyloid in transgenic mice using magnetic resonance microimaging. Magn Reson Med. 2003;50(2):293–302. doi:10.1002/mrm.1052912876705
  • Skaat H, Margel S. Synthesis of fluorescent-maghemite nanoparticles as multimodal imaging agents for amyloid-β fibrils detection and removal by a magnetic field. Biochem Biophys Res Commun. 2009;386(4):645–649. doi:10.1016/j.bbrc.2009.06.11019559008
  • Skaat H, Sorci M, Belfort G, Margel S. Effect of maghemite nanoparticles on insulin amyloid fibril formation: selective labeling, kinetics, and fibril removal by a magnetic field. J Biomed Mater Res Part A. 2009;91(2):342–351. doi:10.1002/jbm.a.32232
  • Siegemund T, Paulke B-R, Schmiedel H, et al. Thioflavins released from nanoparticles target fibrillar amyloid β in the hippocampus of APP/PS1 transgenic mice. Int J Dev Neurosci. 2006;24(2–3):195–201. doi:10.1016/j.ijdevneu.2005.11.01216386399
  • Choi J-S, Choi HJ, Jung DC, Lee J-H, Cheon J. Nanoparticle assisted magnetic resonance imaging of the early reversible stages of amyloid β self-assembly. Chem Commun. 2008;19:2197–2199. doi:10.1039/b803294g
  • Dubertret B, Skourides P, Norris DJ, Noireaux V, Brivanlou AH, Libchaber A. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science. 2002;298(5599):1759–1762. doi:10.1126/science.107719412459582
  • 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. Proc Natl Acad Sci. 2005;102(7):2273–2276. doi:10.1073/pnas.040933610215695586
  • Kolb HC, Finn M, Sharpless KB. Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed. 2001;40(11):2004–2021.
  • Kang D-Y, Lee J-H, Oh B-K, Choi J-W. Ultra-sensitive immunosensor for β-amyloid (1–42) using scanning tunneling microscopy-based electrical detection. Biosens Bioelectron. 2009;24(5):1431–1436. doi:10.1016/j.bios.2008.08.01818829296
  • Tiwari S, Atluri VSR, Yndart Arias A, et al. Withaferin a suppresses beta amyloid in APP expressing cells: studies for tat and cocaine associated neurological dysfunctions. Front Aging Neurosci. 2018;10:291. doi:10.3389/fnagi.2018.0029130356847
  • Hsiao IL, Hsieh YK, Chuang CY, Wang CF, Huang YJ. Effects of silver nanoparticles on the interactions of neuron‐and glia‐like cells: toxicity, uptake mechanisms, and lysosomal tracking. Environ Toxicol. 2017;32(6):1742–1753. doi:10.1002/tox.2239728181394
  • Hsiao I-L, Hsieh Y-K, Wang C-F, Chen I-C, Huang Y-J. Trojan-horse mechanism in the cellular uptake of silver nanoparticles verified by direct intra-and extracellular silver speciation analysis. Environ Sci Technol. 2015;49(6):3813–3821. doi:10.1021/es504705p25692749
  • Leszek J, Md Ashraf G, Tse WH, et al. Nanotechnology for Alzheimer disease. Curr Alzheimer Res. 2017;14(11):1182–1189. doi:10.2174/156720501466617020312500828164767
  • Fernandes J, Ghate MV, Mallik SB, Lewis SA. Amino acid conjugated chitosan nanoparticles for the brain targeting of a model dipeptidyl peptidase-4 inhibitor. Int J Pharm. 2018. doi:10.1016/j.ijpharm.2018.06.031
  • Lammers T, Rizzo LY, Storm G, Kiessling F. Personalized nanomedicine. Clin Cancer Res. 2012;18(18):4889–4894. doi:10.1158/1078-0432.CCR-12-141422829203
  • Tietjen GT, Saltzman WM. Nanomedicine gets personal. Sci Transl Med. 2015;7(314):314fs347. doi:10.1126/scitranslmed.aad3106
  • Yu D, Khan OF, Suvà ML, et al. Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression. Proc Natl Acad Sci. 2017;114(30):E6147-–E6156. doi:10.1073/pnas.1701911114
  • Jayant RD, Atluri VS, Tiwari S, et al. Novel nanoformulation to mitigate co-effects of drugs of abuse and HIV-1 infection: towards the treatment of NeuroAIDS. J Neurovirol. 2017;23(4):603–614. doi:10.1007/s13365-017-0538-828762183
  • Nair M, Jayant RD, Kaushik A, Sagar V. Getting in to the brain: potential of nanotechnology to manage neuroAIDS. Adv Drug Deliv Rev. 2016;103:202–217.
  • Kaushik A, Jayant RD, Nair M. Advancements in nano-enabled therapeutics for neuroHIV management. Int J Nanomedicine. 2016;11:4317. doi:10.2147/IJN.S10994327621624
  • Nair M, Guduru R, Liang P, Hong J, Sagar V, Khizroev S. Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers. Nat Commun. 2013;4:1707. doi:10.1038/ncomms271723591874
  • Veronese FM, Mero A. The impact of PEGylation on biological therapies. BioDrugs. 2008;22(5):315–329. doi:10.2165/00063030-200822050-0000418778113
  • Kang JS, DeLuca PP, Lee KC. Emerging pegylated drugs. Expert Opin Emerg Drugs. 2009;14(2):363–380. doi:10.1517/1472821090290784719453284
  • Kanwal U, Irfan Bukhari N, Ovais M, Abass N, Hussain K, Raza A. Advances in nano-delivery systems for doxorubicin: an updated insight. J Drug Target. 2018;26(4):296–310. doi:10.1080/1061186X.2017.138065528906159
  • Dadashzadeh S, Vali A, Rezaie M. The effect of PEG coating on in vitro cytotoxicity and in vivo disposition of topotecan loaded liposomes in rats. Int J Pharm. 2008;353(1–2):251–259. doi:10.1016/j.ijpharm.2007.11.03018191511
  • Ochi MM, Amoabediny G, Rezayat SM, Akbarzadeh A, Ebrahimi B. In vitro co-delivery evaluation of novel pegylated nano-liposomal herbal drugs of silibinin and glycyrrhizic acid (nano-phytosome) to hepatocellular carcinoma cells. Cell J (Yakhteh). 2016;18(2):135.
  • Stimphil E, Nagesetti A, Guduru R, et al. Physics considerations in targeted anticancer drug delivery by magnetoelectric nanoparticles. Appl Phys Rev. 2017;4(2):021101. doi:10.1063/1.4978642
  • Kaushik A, Jayant RD, Nikkhah-Moshaie R, et al. Magnetically guided central nervous system delivery and toxicity evaluation of magneto-electric nanocarriers. Sci Rep. 2016;6:25309. doi:10.1038/srep2530927143580
  • Hamburg MA, Collins FS. The path to personalized medicine. N Engl J Med. 2010;363(4):301–304. doi:10.1056/NEJMp100630420551152
  • Theek B, Rizzo LY, Ehling J, Kiessling F, Lammers T. The theranostic path to personalized nanomedicine. Clin Transl Imaging. 2014;2(1):67–76. doi:10.1007/s40336-014-0051-5
  • Jain KK, Jain KK. The Handbook of Nanomedicine. Vol. 404 Heidelberg: Springer; 2008.
  • Fornaguera C, García-Celma M. Personalized nanomedicine: a revolution at the nanoscale. J pers med. 2017;7(4):12. doi:10.3390/jpm7040012
  • Mura S, Couvreur P. Nanotheranostics for personalized medicine. Adv Drug Deliv Rev. 2012;64(13):1394–1416. doi:10.1016/j.addr.2012.06.00622728642
  • Yang F-Y, Lin Y-S, Kang K-H, Chao T-K. Reversible blood–brain barrier disruption by repeated transcranial focused ultrasound allows enhanced extravasation. J Control Release. 2011;150(1):111–116. doi:10.1016/j.jconrel.2010.10.03821070825
  • Sanhai WR, Sakamoto JH, Canady R, Ferrari M. Seven challenges for nanomedicine. Nat Nanotechnol. 2008;3(5):242. doi:10.1038/nnano.2008.11418654511
  • Association As. 2014 Alzheimer‘s disease facts and figures. Alzheimer‘S Dementia. 2014;10(2):e47–e92. doi:10.1016/j.jalz.2014.02.001
  • Kaushik A, Jayant RD, Tiwari S, Vashist A, Nair M. Nano-biosensors to detect beta-amyloid for Alzheimer‘s disease management. Biosens Bioelectron. 2016;80:273–287. doi:10.1016/j.bios.2016.01.06526851586
  • Sagar V, Pilakka‐Kanthikeel S, Pottathil R, Saxena SK, Nair M. Towards nanomedicines for neuroAIDS. Rev Med Virol. 2014;24(2):103–124. doi:10.1002/rmv.177824395761