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Review Articles

Novel strategies for the fight of Alzheimer’s disease targeting amyloid-β protein

, , , , &
Pages 259-268 | Received 24 May 2021, Accepted 22 Aug 2021, Published online: 03 Sep 2021

References

  • Hardy J. The amyloid hypothesis for Alzheimer’s disease: a critical reappraisal. J Neurochem. 2009;110(4):1129–1134.
  • Golde TE. Alzheimer disease therapy: can the amyloid Cascade be halted? J Clin Invest. 2003;111(1):11–18.
  • Lapresa R, Agulla J, Sanchez-Moran I, et al. Amyloid-ß promotes neurotoxicity by Cdk5-induced p53 stabilization. Neuropharmacology. 2019;146:19–27.
  • Balcells M, Wallins JS, Edelman ER. Amyloid beta toxicity dependent upon endothelial cell state. Neurosci Lett. 2008;441(3):319–322.
  • Pauwels K, Williams TL, Morris KL, et al. Structural basis for increased toxicity of pathological aβ42:aβ40 ratios in Alzheimer disease. J Biol Chem. 2012;287(8):5650–5660.
  • Ishibashi K-I, Tomiyama T, Nishitsuji K, et al. Absence of synaptophysin near cortical neurons containing oligomer Abeta in Alzheimer’s disease brain. J Neurosci Res. 2006;84(3):632–636.
  • Villemagne VL, Okamura N. In vivo tau imaging: obstacles and progress. Alzheimers Dement. 2014;10(3 Suppl):S254–S64.
  • Wenk GL. Neuropathologic changes in Alzheimer’s disease: potential targets for treatment. J Clin Psych. 2006;67:3–7.
  • Bateman RJ, Xiong CJ, Benzinger TLS, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012;367(9):795–804.
  • Villemagne VL, Burnham S, Bourgeat P, et al. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol. 2013;12(4):357–367.
  • Zhang W, Oya S, Kung MP, et al. F-18 stilbenes as PET imaging agents for detecting beta-amyloid plaques in the brain. J Med Chem. 2005;48(19):5980–5988.
  • Bateman RJ, Siemers ER, Mawuenyega KG, et al. A gamma-secretase inhibitor decreases amyloid-beta production in the Central nervous system. Ann Neurol. 2009;66(1):48–54.
  • Lin XL, Koelsch C, Wu SL, et al. Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein. Proc Natl Acad Sci USA. 2000;97(4):1456–1460.
  • Pithadia AS, Lim MH. Metal-associated amyloid-β species in Alzheimer’s disease. Curr Opin Chem Biol. 2012;16(1–2):67–73.
  • Faller P, Hureau C, La Penna G. Metal ions and intrinsically disordered proteins and peptides: from Cu/Zn amyloid-β to general principles. Acc Chem Res. 2014;47(8):2252–2259.
  • Chen W-T, Liao Y-H, Yu H-M, et al. Distinct effects of Zn2+, Cu2+, Fe3+, and Al3+ on amyloid-beta stability, oligomerization, and aggregation: amyloid-beta destabilization promotes annular protofibril formation. J Biol Chem. 2011;286(11):9646–9656.
  • Granzotto A, Zatta P. Resveratrol and Alzheimer’s disease: message in a bottle on red wine and cognition. Front Aging Neurosci. 2014;6:95.
  • House E, Esiri M, Forster G, et al. Aluminium, iron and copper in human brain tissues donated to the medical research council's cognitive function and ageing study. Metallomics. 2012;4(1):56–65.
  • Sparks DL, Schreurs BG. Trace amounts of copper in water induce beta-amyloid plaques and learning deficits in a rabbit model of Alzheimer’s disease. Proc Natl Acad Sci USA. 2003;100(19):11065–11069.
  • Santos MA, Chand K, Chaves S. Recent progress in multifunctional metal chelators as potential drugs for alzheimer's disease. Coord Chem Rev. 2016;327–328:287–303.
  • Tay WM, da Silva GFZ, Ming L-J. Metal binding of flavonoids and their distinct inhibition mechanisms toward the oxidation activity of Cu2+-β-amyloid: not just serving as suicide antioxidants! Inorg Chem. 2013;52(2):679–690.
  • Faller P, Hureau C. Bioinorganic chemistry of copper and zinc ions coordinated to amyloid-beta peptide. Dalton Trans. 2009;(7):1080–1094.
  • Nair NG, Perry G, Smith MA, et al. NMR studies of zinc, copper, and iron binding to histidine, the principal metal ion complexing site of amyloid-beta peptide. J Alzheimers Dis. 2010;20(1):57–66.
  • Cristovao JS, Figueira AJ, Carapeto AP, et al. The S100B Alarmin is a dual-function chaperone suppressing amyloid-β oligomerization through combined zinc chelation and inhibition of protein aggregation. ACS Chem Neurosci. 2020;11(17):2753–2760.
  • Vicente-Zurdo D, Romero-Sanchez I, Rosales-Conrado N, et al. Ability of selenium species to inhibit metal-induced Aβ aggregation involved in the development of Alzheimer’s disease. Anal Bioanal Chem. 2020;412(24):6485–6497.
  • Oh SB, Kim JA, Park S, et al. Associative interactions among zinc, apolipoprotein E, and amyloid-beta in the amyloid pathology. Int J Mol Sci. 2020;21(3):802.
  • Adlard PA, Cherny RA, Finkelstein DI, et al. Rapid restoration of cognition in Alzheimer’s transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta. Neuron. 2008;59(1):43–55.
  • Jenagaratnam L, McShane R. Clioquinol for the treatment of Alzheimer’s disease. Cochrane Database Syst Rev. 2006;(1):CD005380.
  • Villemagne VL, Rowe CC, Barnham KJ, et al. A randomized, exploratory molecular imaging study targeting amyloid beta with a novel 8-OH quinoline in Alzheimer’s disease: the PBT2-204 IMAGINE study. Alzheimer’s. Dementia Y. 2017;3(4):622–635.
  • Khan AN, Hassan MN, Khan RH. Gallic acid: a naturally occurring bifunctional inhibitor of amyloid and metal induced aggregation with possible implication in metal-based therapy. J Mol Liq. 2019;285:27–37.
  • Zou Z, Cai J, Zhong A, et al. Using the synthesized peptide HAYED (5) to protect the brain against iron catalyzed radical attack in a naturally senescence Kunming mouse model. Free Radic Biol Med. 2019;130:458–470.
  • Barnham KJ, Kenche VB, Ciccotosto GD, et al. Platinum-based inhibitors of amyloid-beta as therapeutic agents for Alzheimer’s disease. Proc Natl Acad Sci USA. 2008;105(19):6813–6818.
  • Kenche VB, Hung LW, Perez K, et al. Development of a platinum complex as an anti-Amyloid agent for the therapy of alzheimer's disease. Angew Chem Int Ed Engl. 2013;52(12):3374–3378.
  • 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.
  • Glenner GG, Wong CW. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid proteindisease. Biochem Biophys Res Commun. 1984;120(3):885–890.
  • Chen G-F, Xu T-h, Yan Y, et al. Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol Sin. 2017;38(9):1205–1235.
  • Eisenberg D, Jucker M. The amyloid state of proteins in human diseases. Cell. 2012;148(6):1188–1203.
  • Balbach JJ, Petkova AT, Oyler NA, et al. Supramolecular structure in full-length Alzheimer’s beta-amyloid fibrils: evidence for a parallel beta-sheet organization from solid-state nuclear magnetic resonance. Biophys J. 2002;83(2):1205–1216.
  • Petkova AT, Buntkowsky G, Dyda F, et al. Solid state NMR reveals a pH-dependent antiparallel beta-sheet registry in fibrils formed by a beta-amyloid peptide. J Mol Biol. 2004;335(1):247–260.
  • Kayed R, Head E, Thompson JL, et al. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science. 2003;300(5618):486–489.
  • Walsh DM, Klyubin I, Fadeeva JV, et al. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature. 2002;416(6880):535–539.
  • Ahmed M, Davis J, Aucoin D, et al. Structural conversion of neurotoxic amyloid-beta(1–42) oligomers to fibrils. Nat Struct Mol Biol. 2010;17(5):561–U56.
  • Haass C, Schlossmacher MG, Hung AY, et al. Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature. 1992;359(6393):322–325.
  • 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.
  • Crescenzi O, Tomaselli S, Guerrini R, et al. Solution structure of the Alzheimer amyloid beta-peptide (1–42) in an apolar microenvironment: similarity with a virus fusion domain. Eur J Biochem. 2002;269(22):5642–5648.
  • Sgourakis NG, Merced-Serrano M, Boutsidis C, et al. Atomic-level characterization of the ensemble of the Aβ(1–42) monomer in water using unbiased molecular dynamics simulations and spectral algorithms. J Mol Biol. 2011;405(2):570–583.
  • Sgourakis NG, Yan Y, McCallum SA, et al. The Alzheimer’s peptides Abeta40 and 42 adopt distinct conformations in water: a combined MD/NMR study. J Mol Biol. 2007;368(5):1448–1457.
  • Guerreiro RJ, Gustafson DR, Hardy J. The genetic architecture of Alzheimer’s disease: beyond APP, PSENs and APOE. Neurobiol Aging. 2012;33(3):437–456.
  • Games D, Adams D, Alessandrini R, et al. Alzheimer-type neuropathology in transgenic mice overexpressing v717f beta-amyloid precursor protein. Nature. 1995;373(6514):523–527.
  • Suarez-Calvet M, Belbin O, Pera M, et al. Autosomal-dominant Alzheimer’s disease mutations at the same codon of amyloid precursor protein differentially alter Aβ production. J Neurochem. 2014;128(2):330–339.
  • Du Z, Li M, Ren J, et al. Current strategies for modulating Aβ Aggregation with multifunctional agents. Acc Chem Res. 2021;54(9):2172–2184.
  • Asai M, Hattori C, Iwata N, et al. The novel beta-secretase inhibitor KMI-429 reduces amyloid beta peptide production in amyloid precursor protein transgenic and wild-type mice. J Neurochem. 2006;96(2):533–540.
  • Min KC, Dockendorf MF, Palcza J, et al. Pharmacokinetics and pharmacodynamics of the BACE1 inhibitor verubecestat (MK-8931) in healthy Japanese adults: a randomized, Placebo-Controlled study. Clin Pharmacol Ther. 2019;105(5):1234–1243.
  • Cebers G, Alexander RC, Haeberlein SB, et al. AZD3293: pharmacokinetic and pharmacodynamic effects in healthy subjects and patients with Alzheimer’s Disease. J Alzheimers Dis. 2017;55(3):1039–1053.
  • Chang W-P, Huang X, Downs D, et al. beta-Secretase inhibitor GRL-8234 rescues age-related cognitive decline in APP transgenic mice. Faseb J. 2011;25(2):775–784.
  • Kounnas MZ, Lane-Donovan C, Nowakowski DW, et al. NGP 555, a γ-secretase modulator, lowers the amyloid biomarker, Aβ42, in cerebrospinal fluid while preventing Alzheimer’s Disease Cognitive Decline in Rodents. Alzheimers Dement. 2017;3(1):65–73.
  • Scannevin RH, Chollate S, Brennan MS, et al. BIIB042, a novel γ-secretase modulator, reduces amyloidogenic Aβ isoforms in primates and rodents and plaque pathology in a mouse model of Alzheimer’s disease. Neuropharmacology. 2016;103:57–68.
  • Henley D, Raghavan N, Sperling R, et al. Preliminary results of a trial of atabecestat in preclinical Alzheimer’s disease. N Engl J Med. 2019;380(15):1483–1485.
  • Imbimbo BP, Panza F, Frisardi V, et al. Therapeutic intervention for Alzheimer’s disease with γ-secretase inhibitors: still a viable option? Expert Opin Investig Drugs. 2011;20(3):325–341.
  • Mjos KD, Orvig C. Metallodrugs in medicinal inorganic chemistry. Chem Rev. 2014;114(8):4540–4563.
  • Smith DP, Smith DG, Curtain CC, et al. Copper-mediated amyloid-beta toxicity is associated with an intermolecular histidine bridge. J Biol Chem. 2006;281(22):15145–15154.
  • Telpoukhovskaia MA, Orvig C. Werner coordination chemistry and neurodegeneration. Chem Soc Rev. 2013;42(4):1836–1846.
  • Wang X, Wang X, Zhang C, et al. Inhibitory action of macrocyclic platiniferous chelators on metal-induced a beta aggregation. Chem Sci. 2012;3(4):1304–1312.
  • Bataglioli JC, Gomes LMF, Maunoir C, Smith JR, et al. Modification of amyloid-beta peptide aggregation via photoactivation of strained Ru(ii) polypyridyl complexes. Chem Sci. 2021;12(21):7510–7520.
  • Huffman SE, Yawson GK, Fisher SS, et al. Ruthenium(III) complexes containing thiazole-based ligands that modulate amyloid-β aggregation. Metallomics. 2020;12(4):491–503.
  • Messori L, Camarri M, Ferraro T, et al. Promising in vitro anti-Alzheimer properties for a ruthenium(III) complex. ACS Med Chem Lett. 2013;4(3):329–332.
  • Vyas NA, Ramteke SN, Kumbhar AS, et al. Ruthenium(II) polypyridyl complexes with hydrophobic ancillary ligand as Aβ aggregation inhibitors. Eur J Med Chem. 2016;121:793–802.
  • Jones MR, Mu C, Wang MCP, et al. Modulation of the Aβ peptide aggregation pathway by KP1019 limits Aβ-associated neurotoxicity. Metallomics. 2015;7(1):129–135.
  • Gomes LMF, Bataglioli JC, Jussila AJ, Smith JR, et al. Modification of Aβ peptide aggregation via covalent binding of a series of Ru(III) complexes. Front Chem. 2019;7:838.
  • Kang J, Lee SJC, Nam JS, et al. An iridium(III) complex as a photoactivatable tool for oxidation of amyloidogenic peptides with subsequent modulation of peptide aggregation. Chemistry. 2017;23(7):1645–1653.
  • Iscen A, Brue CR, Roberts KF, et al. Inhibition of amyloid-β aggregation by Cobalt(III) schiff base complexes: a computational and experimental approach. J Am Chem Soc. 2019;141(42):16685–16695.
  • Yu H, Li M, Liu G, et al. Metallosupramolecular complex targeting an alpha/beta discordant stretch of amyloid beta peptide. Chem Sci. 2012;3(11):3145–3153.
  • Li M, Zhao C, Duan T, et al. New insights into Alzheimer’s disease amyloid inhibition: nanosized metallo-supramolecular complexes suppress aβ-induced biosynthesis of heme and iron uptake in PC12 cells. Adv Healthc Mater. 2014;3(6):832–836.
  • Li M, Howson SE, Dong K, et al. Chiral metallohelical complexes enantioselectively target amyloid β for treating Alzheimer’s disease. J Am Chem Soc. 2014;136(33):11655–11663.
  • Guan Y, Du Z, Gao N, et al. Stereochemistry and amyloid inhibition: asymmetric triplex metallohelices enantioselectively bind to Aβ peptide. Sci Adv. 2018;4(1):eaao6718.
  • D’Acunto CW, Kaplanek R, Gbelcova H, et al. Metallomics for Alzheimer’s disease treatment: use of new generation of chelators combining metal-cation binding and transport properties. Eur J Med Chem. 2018;150:140–155.
  • Palanimuthu D, Wu Z, Jansson PJ, et al. Novel chelators based on adamantane-derived semicarbazones and hydrazones that target multiple hallmarks of Alzheimer’s disease. Dalton Trans. 2018;47(21):7190–7205.
  • Swetha R, Kumar D, Gupta SK, et al. Multifunctional hybrid sulfonamides as novel therapeutic agents for Alzheimer’s disease. Future Med Chem. 2019;11(24):3161–3177.
  • Piemontese L, Tomas D, Hiremathad A, et al. M: Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer’s drug candidates. J Enzyme Inhib Med Chem. 2018;33(1):1212–1224.
  • Asadbegi M, Shamloo A. Identification of a novel multifunctional ligand for simultaneous inhibition of Amyloid-Beta (Aβ42) and Chelation of Zinc Metal Ion. ACS Chem Neurosci. 2019;10(11):4619–4632.
  • Mishra CB, Gusain S, Shalini S, et al. Development of novel carbazole derivatives with effective multifunctional action against Alzheimer’s diseases: design, synthesis, in silico, in vitro and in vivo investigation. Bioorg Chem. 2020;95:103524.
  • Han J, Lee HJ, Kim KY, et al. Mechanistic approaches for chemically modifying the coordination sphere of copper-amyloid-β complexes. Proc Natl Acad Sci USA. 2020;117(10):5160–5167.
  • Du Z, Yu D, Du X, et al. Self-triggered click reaction in an Alzheimer’s disease model: in situ bifunctional drug synthesis catalyzed by neurotoxic copper accumulated in amyloid-β plaques. Chem Sci. 2019;10(44):10343–10350.
  • Li M, Shi P, Xu C, et al. Cerium oxide caged metal chelator: anti-aggregation and anti-oxidation integrated H2O2-responsive controlled drug release for potential Alzheimer’s disease treatment. Chem Sci. 2013;4(6):2536–2542.
  • Li M, Guan Y, Ding C, et al. An ultrathin graphitic carbon nitride nanosheet: a novel inhibitor of metal-induced amyloid aggregation associated with Alzheimer’s disease. J Mater Chem B. 2016;4(23):4072–4075.
  • Li M, Liu Z, Ren J, et al. Inhibition of metal-induced amyloid aggregation using light-responsive magnetic nanoparticle prochelator conjugates. Chem Sci. 2012;3(3):868–873.
  • Guan Y, Gao N, Ren J, et al. Rationally designed CeNP@MnMoS4 core-shell nanoparticles for modulating multiple facets of Alzheimer’s disease. Chemistry-a. Chemistry. 2016;22(41):14523–14526.
  • Geng J, Li M, Wu L, et al. Liberation of copper from amyloid plaques: making a risk factor useful for Alzheimer’s disease treatment. J Med Chem. 2012;55(21):9146–9155.
  • Gupta SC, Prasad S, Kim JH, et al. Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep. 2011;28(12):1937–1955.
  • Summers KL, Roseman GP, Sopasis GJ, et al. Copper(II) binding to PBT2 differs from that of other 8-Hydroxyquinoline chelators: implications for the treatment of neurodegenerative protein misfolding diseases. Inorg Chem. 2020;59(23):17519–17534.
  • Loureiro JC, Pais MV, Stella F, et al. Passive antiamyloid immunotherapy for Alzheimer’s disease. Curr Opin Psychiatry. 2020;33(3):284–291.
  • Schwartz M, Ramos JMP, Ben-Yehuda H. A 20-Year journey from axonal injury to neurodegenerative diseases and the prospect of immunotherapy for combating Alzheimer’s disease. J Immunol. 2020;204(2):243–250.
  • Gilman S, Koller M, Black RS, Jenkins L, et al. Team as: clinical effects of a beta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005;64(9):1553–1562.
  • Brashear HR, Ketter N, Bogert J, et al. Clinical evaluation of amyloid-related imaging abnormalities in bapineuzumab phase III studies. J Alzheimers Dis. 2018;66(4):1409–1424.
  • Imbimbo BP, Ottonello S, Frisardi V, et al. Solanezumab for the treatment of mild-to-moderate alzheimer's disease. Expert Rev Clin Immunol. 2012;8(2):135–149.
  • Doggrell SA. Grasping at straws: the failure of solanezumab to modify mild Alzheimer’s disease. Expert Opin Biol Ther. 2018;18(12):1189–1192.
  • Blennow K, Zetterberg H, Rinne JO, et al. Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels in patients with mild to moderate alzheimer disease. Arch Neurol. 2012;69(8):1002–1010.
  • Lemere CA. Immunotherapy for Alzheimer’s disease: hoops and hurdles. Mol Neurodegener. 2013;8:36.
  • Tayeb HO, Murray ED, Price BH, et al. Bapineuzumab and solanezumab for Alzheimer’s disease: is the ‘amyloid Cascade hypothesis’ still alive? Expert Opin Biol Ther. 2013;13(7):1075–1084.
  • Siemers ER, Sundell KL, Carlson C, et al. Phase 3 solanezumab trials: secondary outcomes in mild Alzheimer’s disease patients. Alzheimers Dement. 2016;12(2):110–120.
  • 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-a beta protofibril antibody. Alzheimers Res Ther. 2021;2021:13.
  • Lowe SL, Willis BA, Hawdon A, et al. Donanemab (LY3002813) dose-escalation study in Alzheimer’s disease. Alzheimer’s Dementia. 2021;7:e12112.
  • Mintun MA, Lo AC, Evans CD, et al. Donanemab in early Alzheimer’s disease. N Engl J Med. 2021;384(18):1691–1704.
  • Bastrup J, Hansen KH, Poulsen TBG, et al. Anti-Aβ Antibody aducanumab regulates the proteome of senile plaques and closely surrounding tissue in a transgenic mouse model of Alzheimer’s Disease. J Alzheimers Dis. 2021;79(1):249–265.
  • Vaillancourt DE. Aducanumab reduces Aβ plaques in Alzheimer’s disease. Mov Disord. 2016;31(11):1631.
  • Schneider L. A resurrection of aducanumab for Alzheimer’s disease. Lancet Neurol. 2020;19(2):111–112.
  • Yang P, Sun F. Aducanumab: the first targeted Alzheimer’s therapy. Drug Discov Ther. 2021;15(3):166–168.
  • Balducci C, Forloni G. Doxycycline for Alzheimer’s disease: fighting β-Amyloid Oligomers and Neuroinflammation. Front Pharmacol. 2019;10:738.
  • Molloy DW, Standish TI, Zhou Q, et al. A multicenter, blinded, randomized, factorial controlled trial of doxycycline and rifampin for treatment of Alzheimer’s disease: the DARAD trial. Int J Geriatr Psychiatry. 2013;28(5):463–470.
  • Lundebjerg NE. My head just exploded, now what? Aducanumab. J Am Geriatr Soc. 2021;2021:17350.
  • Fillit H, Green A. Aducanumab and the FDA – where are we now? Nat Rev Neurol. 2021;17(3):129–130.
  • Ju Y, Tam KY. 9R, the cholinesterase and amyloid beta aggregation dual inhibitor, as a multifunctional agent to improve cognitive deficit and neuropathology in the triple-transgenic alzheimer's disease mouse model. Neuropharmacology. 2020;181:108354.
  • Wang X, Sun G, Feng T, et al. Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression. Cell Res. 2019;29(10):787–803.
  • Wang T, Kuang W, Chen W, et al. A phase ii randomized trial of sodium oligomannate in Alzheimer’s Dementia. Alzheimers Res Ther. 2020;12(1):110.
  • Perrin RJ, Fagan AM, Holtzman DM. Multimodal techniques for diagnosis and prognosis of Alzheimer’s disease. Nature. 2009;461(7266):916–922.
  • Ono M, Saji H. Recent advances in molecular imaging probes for beta-amyloid plaques. Med Chem Commun. 2015;6(3):391–402.
  • Sagnou M, Mavroidi B, Shegani A, et al. Remarkable brain penetration of cyclopentadienyl M(CO)3+ (M = 99mTc, Re) Derivatives of Benzothiazole and Benzimidazole Paves the Way for Their Application as Diagnostic, with Single-Photon-Emission Computed Tomography (SPECT), and Therapeutic Agents for Alzheimer’s Disease. J Med Chem. 2019;62(5):2638–2650.
  • Li T-R, Wu Y, Jiang J-J, et al. Radiomics analysis of magnetic resonance imaging facilitates the identification of preclinical Alzheimer’s disease: an exploratory study. Front Cell Dev Biol. 2020;8:605734.
  • Li C, Yang L, Han Y, et al. A simple approach to quantitative determination of soluble amyloid-beta peptides using a ratiometric fluorescence probe. Biosensors Bioelectronics. 2019;142:111518.

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