{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:16:49Z","timestamp":1791487009030,"version":"4.3.4"},"reference-count":83,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060661,81660151 and 81660751"],"award-info":[{"award-number":["82060661,81660151 and 81660751"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The amyloid hypothesis of Alzheimer\u2019s disease has long been the predominant theory, suggesting that Alzheimer\u2019s disease is caused by the accumulation of amyloid beta protein (A\u03b2) in the brain, leading to neuronal toxicity in the central nervous system (CNS). Because of breakthroughs in molecular medicine, the amyloid pathway is thought to be central to the pathophysiology of Alzheimer\u2019s disease (AD). Currently, it is believed that altered biochemistry of the A\u03b2 cycle remains a central biological feature of AD and is a promising target for treatment. This review provides an overview of the process of amyloid formation, explaining the transition from amyloid precursor protein to amyloid beta protein. Moreover, we also reveal the relationship between autophagy, cerebral blood flow, ACHE, expression of LRP1, and amyloidosis. In addition, we discuss the detailed pathogenesis of amyloidosis, including oxidative damage, tau protein, NFTs, and neuronal damage. Finally, we list some ways to treat AD in terms of decreasing the accumulation of A\u03b2 in the brain.<\/jats:p>","DOI":"10.3390\/molecules27041210","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T20:34:45Z","timestamp":1644784485000},"page":"1210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":221,"title":["Amyloidosis in Alzheimer\u2019s Disease: Pathogeny, Etiology, and Related Therapeutic Directions"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6380-0043","authenticated-orcid":false,"given":"Chen","family":"Ma","sequence":"first","affiliation":[{"name":"Experimental Center of Pathogen Biology, Nanchang University, Nanchang 330006, China"},{"name":"Queen Marry College, School of Medicine, Nanchang University, Nanchang 330036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenfang","family":"Hong","sequence":"additional","affiliation":[{"name":"Experimental Center of Pathogen Biology, Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Nanchang University, Nanchang 330006, China"},{"name":"Department of Physiology, Fuzhou Medical College, Nanchang University, Nanchang 344099, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","article-title":"Alzheimer Disease: An Update on Pathobiology and Treatment Strategies","volume":"179","author":"Long","year":"2019","journal-title":"Cell"},{"key":"ref_2","unstructured":"Prince, M.J., Wimo, A., Guerchet, M.M., Ali, G.C., Wu, Y.-T., and Prina, M. (2015). World Alzheimer Report 2015\u2014The Global Impact of Dementia: An Analysis of Prevalence, Incidence, Cost and Trends, Alzheimer\u2019s Disease International."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"772068","DOI":"10.3389\/fpsyt.2021.772068","article-title":"Brain Functional and Structural Changes in Alzheimer\u2019s Disease With Sleep Disorders: A Systematic Review","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"112435","DOI":"10.1016\/j.bbr.2019.112435","article-title":"Changes in brain activation related to visuo-spatial memory after real-time fMRI neurofeedback training in healthy elderly and Alzheimer\u2019s disease","volume":"381","author":"Hohenfeld","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.jalz.2007.04.381","article-title":"Forecasting the global burden of Alzheimer\u2019s disease","volume":"3","author":"Brookmeyer","year":"2007","journal-title":"Alzheimers Dement."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1001\/jama.2019.4782","article-title":"Diagnosis and Management of Dementia: Review","volume":"322","author":"Arvanitakis","year":"2019","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.jalz.2016.03.001","article-title":"2016 Alzheimer\u2019s disease facts and figures","volume":"12","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104852","DOI":"10.1016\/j.neuint.2020.104852","article-title":"Environmental toxins and Alzheimer\u2019s disease progression","volume":"141","author":"Vasefi","year":"2020","journal-title":"Neurochem. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"631","DOI":"10.3233\/JAD-170062","article-title":"State of Play in Alzheimer\u2019s Disease Genetics","volume":"58","author":"Zhu","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"413808","DOI":"10.1155\/2013\/413808","article-title":"Amyloidosis in Alzheimer\u2019s Disease: The Toxicity of Amyloid Beta (A\u03b2), Mechanisms of Its Accumulation and Implications of Medicinal Plants for Therapy","volume":"2013","author":"Prasansuklab","year":"2013","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.3389\/fnins.2019.01154","article-title":"The Beta Amyloid Dysfunction (BAD) Hypothesis for Alzheimer\u2019s Disease","volume":"13","author":"Hillen","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1002\/mds.26624","article-title":"Oligomeropathies and pathogenesis of Alzheimer and Parkinson\u2019s diseases","volume":"31","author":"Forloni","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1080\/13506120701460923","article-title":"A primer of amyloid nomenclature","volume":"14","author":"Westermark","year":"2007","journal-title":"Amyloid"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.bbrc.2012.08.020","article-title":"Alzheimer\u2019s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. 1984","volume":"425","author":"Glenner","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1056\/NEJMra023144","article-title":"Molecular mechanisms of amyloidosis","volume":"349","author":"Merlini","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rice, H.C., de Malmazet, D., Schreurs, A., Frere, S., Van Molle, I., Volkov, A.N., Creemers, E., Vertkin, I., Nys, J., and Ranaivoson, F.M. (2019). Secreted amyloid-beta precursor protein functions as a GABABR1a ligand to modulate synaptic transmission. Science, 363.","DOI":"10.1126\/science.aao4827"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1146\/annurev-neuro-061010-113613","article-title":"Amyloid precursor protein processing and Alzheimer\u2019s disease","volume":"34","author":"Wong","year":"2011","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29615","DOI":"10.1074\/jbc.R800019200","article-title":"Amyloid precursor protein trafficking, processing, and function","volume":"283","author":"Thinakaran","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0140-6736(06)69113-7","article-title":"Alzheimer\u2019s disease","volume":"368","author":"Blennow","year":"2006","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00401-016-1558-9","article-title":"Presynaptic dystrophic neurites surrounding amyloid plaques are sites of microtubule disruption, BACE1 elevation, and increased Abeta generation in Alzheimer\u2019s disease","volume":"132","author":"Sadleir","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1016\/j.febslet.2013.05.010","article-title":"The amyloid precursor protein: A biochemical enigma in brain development, function and disease","volume":"587","author":"Nalivaeva","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1046\/j.1365-2990.1999.00164.x","article-title":"The amyloid precursor protein of Alzheimer\u2019s disease and the Abeta peptide","volume":"25","author":"Storey","year":"1999","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_24","first-page":"1558","article-title":"Genetic factors and a polygenic model of Alzheimer\u2019s disease","volume":"35","author":"Rogaev","year":"1999","journal-title":"Genetika"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100281","DOI":"10.1016\/j.jbc.2021.100281","article-title":"Familial Alzheimer\u2019s disease mutations in amyloid protein precursor alter proteolysis by gamma-secretase to increase amyloid beta-peptides of >\/=45 residues","volume":"296","author":"Devkota","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0896-6273(01)00475-5","article-title":"Clearing the brain\u2019s amyloid cobwebs","volume":"32","author":"Selkoe","year":"2001","journal-title":"Neuron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/nm890","article-title":"RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain","volume":"9","author":"Deane","year":"2003","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"16","DOI":"10.2174\/187152709787601867","article-title":"Clearance of amyloid-beta peptide across the blood-brain barrier: Implication for therapies in Alzheimer\u2019s disease","volume":"8","author":"Deane","year":"2009","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3","DOI":"10.17116\/jnevro2016116623-9","article-title":"Twenty-five years of the amyloid hypothesis of alzheimer disease: Advances, failures and new perspectives","volume":"116","author":"Levin","year":"2016","journal-title":"Zh. Nevrol. Psikhiatr. Im. SS Korsakova"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.1097\/00001756-199909290-00017","article-title":"Primary cultures of neuronal and non-neuronal rat brain cells secrete similar proportions of amyloid beta peptides ending at A beta40 and A beta42","volume":"10","author":"Fukumoto","year":"1999","journal-title":"Neuroreport"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3389\/fneur.2013.00079","article-title":"Amyloid-beta Peptides and Tau Protein as Biomarkers in Cerebrospinal and Interstitial Fluid Following Traumatic Brain Injury: A Review of Experimental and Clinical Studies","volume":"4","author":"Tsitsopoulos","year":"2013","journal-title":"Front. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3233\/JAD-131562","article-title":"Activation of neuronal defense mechanisms in response to pathogenic factors triggering induction of amyloidosis in Alzheimer\u2019s disease","volume":"40","author":"Maltsev","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s13238-011-1047-9","article-title":"APP and APLP1 are degraded through autophagy in response to proteasome inhibition in neuronal cells","volume":"2","author":"Zhou","year":"2011","journal-title":"Protein. Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1242\/jcs.019265","article-title":"Autophagy, amyloidogenesis and Alzheimer disease","volume":"120","author":"Nixon","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"502","DOI":"10.4161\/auto.5.4.8096","article-title":"Autophagy protects neuron from Abeta-induced cytotoxicity","volume":"5","author":"Hung","year":"2009","journal-title":"Autophagy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4428","DOI":"10.1021\/acschemneuro.1c00468","article-title":"SIRT5 Represses Neurotrophic Pathways and Abeta Production in Alzheimer\u2019s Disease by Targeting Autophagy","volume":"12","author":"Wu","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3233\/JAD-200843","article-title":"Quantitative Study of the Changes in Cerebral Blood Flow and Iron Deposition During Progression of Alzheimer\u2019s Disease","volume":"78","author":"Li","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1002\/jmri.26810","article-title":"Increased cerebral blood flow with increased amyloid burden in the preclinical phase of alzheimer\u2019s disease","volume":"51","author":"Fazlollahi","year":"2020","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.archger.2012.06.016","article-title":"Walking stabilizes cognitive functioning in Alzheimer\u2019s disease (AD) across one year","volume":"56","author":"Winchester","year":"2013","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"23024","DOI":"10.1074\/jbc.M112.367011","article-title":"Exercise is more effective than diet control in preventing high fat diet-induced beta-amyloid deposition and memory deficit in amyloid precursor protein transgenic mice","volume":"287","author":"Maesako","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.nbd.2012.06.011","article-title":"Exercise counteracts declining hippocampal function in aging and Alzheimer\u2019s disease","volume":"57","author":"Intlekofer","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.3233\/JAD-190729","article-title":"Resistance Exercise Decreases Amyloid Load and Modulates Inflammatory Responses in the APP\/PS1 Mouse Model for Alzheimer\u2019s Disease","volume":"73","author":"Hashiguchi","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6740","DOI":"10.1523\/JNEUROSCI.23-17-06740.2003","article-title":"Beta-amyloid regulation of presynaptic nicotinic receptors in rat hippocampus and neocortex","volume":"23","author":"Dougherty","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"25056","DOI":"10.1074\/jbc.M200066200","article-title":"beta-Amyloid peptide activates alpha 7 nicotinic acetylcholine receptors expressed in Xenopus oocytes","volume":"277","author":"Dineley","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.2174\/13816128113199990503","article-title":"Dangerous liaisons between beta-amyloid and cholinergic neurotransmission","volume":"20","author":"Govoni","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_47","first-page":"294","article-title":"ASS234, As a New Multi-Target Directed Propargylamine for Alzheimer\u2019s Disease Therapy","volume":"10","author":"Unzeta","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"953","DOI":"10.4155\/fmc-2017-0039","article-title":"Multitarget drug design strategy in Alzheimer\u2019s disease: Focus on cholinergic transmission and amyloid-beta aggregation","volume":"9","author":"Simoni","year":"2017","journal-title":"Future Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s00401-006-0115-3","article-title":"RAGE, LRP-1, and amyloid-beta protein in Alzheimer\u2019s disease","volume":"112","author":"Donahue","year":"2006","journal-title":"Acta Neuropathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1038\/nm1635","article-title":"Clearance of amyloid-beta by circulating lipoprotein receptors","volume":"13","author":"Sagare","year":"2007","journal-title":"Nat. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"314ra184","DOI":"10.1126\/scitranslmed.aad1904","article-title":"The E3 ubiquitin ligase Idol controls brain LDL receptor expression, ApoE clearance, and Abeta amyloidosis","volume":"7","author":"Choi","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Fuentealba, R.A., Liu, Q., Zhang, J., Kanekiyo, T., Hu, X., Lee, J.M., LaDu, M.J., and Bu, G. (2010). Low-density lipoprotein receptor-related protein 1 (LRP1) mediates neuronal Abeta42 uptake and lysosomal trafficking. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011884"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"428","DOI":"10.2174\/1567205018666210906092940","article-title":"Effect of High Cholesterol Regulation of LRP1 and RAGE on Abeta Transport Across the Blood-Brain Barrier in Alzheimer\u2019s Disease","volume":"18","author":"Zhou","year":"2021","journal-title":"Curr. Alzheimer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1093\/hmg\/ddy017","article-title":"RAGE mediates Abeta accumulation in a mouse model of Alzheimer\u2019s disease via modulation of beta- and gamma-secretase activity","volume":"27","author":"Fang","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"108304","DOI":"10.1016\/j.neuropharm.2020.108304","article-title":"RP1, a RAGE antagonist peptide, can improve memory impairment and reduce Abeta plaque load in the APP\/PS1 mouse model of Alzheimer\u2019s disease","volume":"180","author":"Huang","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1111\/j.1471-4159.2006.03907.x","article-title":"Oxidative stress and neurodegeneration: Where are we now?","volume":"97","author":"Halliwell","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13195-019-0578-9","article-title":"Nrf2 activation through the PI3K\/GSK-3 axis protects neuronal cells from Abeta-mediated oxidative and metabolic damage","volume":"12","author":"Sotolongo","year":"2020","journal-title":"Alzheimers Res. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.freeradbiomed.2014.06.006","article-title":"The 2013 SFRBM discovery award: Selected discoveries from the butterfield laboratory of oxidative stress and its sequela in brain in cognitive disorders exemplified by Alzheimer disease and chemotherapy induced cognitive impairment","volume":"74","author":"Butterfield","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.bbalip.2010.02.005","article-title":"Involvements of the lipid peroxidation product, HNE, in the pathogenesis and progression of Alzheimer\u2019s disease","volume":"1801","author":"Butterfield","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/S0891-5849(02)00794-3","article-title":"Lipid peroxidation and protein oxidation in Alzheimer\u2019s disease brain: Potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress","volume":"32","author":"Butterfield","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1038\/s42003-021-02551-x","article-title":"Abeta initiates brain hypometabolism, network dysfunction and behavioral abnormalities via NOX2-induced oxidative stress in mice","volume":"4","author":"Malkov","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1161\/STROKEAHA.120.031073","article-title":"Abeta (Amyloid Beta) and Tau Tangle Pathology Modifies the Association Between Small Vessel Disease and Cortical Microinfarcts","volume":"52","author":"Kapasi","year":"2021","journal-title":"Stroke"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.2353\/ajpath.2010.100346","article-title":"A{beta} accelerates the spatiotemporal progression of tau pathology and augments tau amyloidosis in an Alzheimer mouse model","volume":"177","author":"Hurtado","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5092","DOI":"10.1096\/fj.201902230RR","article-title":"Abeta monomer induces phosphorylation of Tau at Ser-214 through beta2AR-PKA-JNK signaling pathway","volume":"34","author":"Wu","year":"2020","journal-title":"FASEB J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2015.11.028","article-title":"Mislocalization of neuronal tau in the absence of tangle pathology in phosphomutant tau knockin mice","volume":"39","author":"Gilley","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13024-021-00460-5","article-title":"\u201cDon\u2019t Phos Over Tau\u201d: Recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer\u2019s disease and other tauopathies","volume":"16","author":"Xia","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1177\/1533317508328602","article-title":"Current concepts in Alzheimer\u2019s disease: A multidisciplinary review","volume":"24","author":"Minati","year":"2009","journal-title":"Am. J. Alzheimers Dis. Other Demen."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1255555","DOI":"10.1126\/science.1255555","article-title":"Neurodegeneration. Alzheimer\u2019s and Parkinson\u2019s diseases: The prion concept in relation to assembled Abeta, tau, and alpha-synuclein","volume":"349","author":"Goedert","year":"2015","journal-title":"Science"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/416535a","article-title":"Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo","volume":"416","author":"Walsh","year":"2002","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/nm1782","article-title":"Amyloid-beta protein dimers isolated directly from Alzheimer\u2019s brains impair synaptic plasticity and memory","volume":"14","author":"Shankar","year":"2008","journal-title":"Nat. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1074\/jbc.M109.030023","article-title":"Beta-amyloid causes depletion of synaptic vesicles leading to neurotransmission failure","volume":"285","author":"Parodi","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Sepulveda, F.J., Parodi, J., Peoples, R.W., Opazo, C., and Aguayo, L.G. (2010). Synaptotoxicity of Alzheimer beta amyloid can be explained by its membrane perforating property. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011820"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1016\/j.neurobiolaging.2013.06.001","article-title":"Inhibition of amyloid beta-induced synaptotoxicity by a pentapeptide derived from the glycine zipper region of the neurotoxic peptide","volume":"34","author":"Peters","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1089\/ars.2011.4277","article-title":"Synaptic mitochondrial pathology in Alzheimer\u2019s disease","volume":"16","author":"Du","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/ana.25562","article-title":"Early A\u03b2 reduction prevents progression of cerebral amyloid angiopathy","volume":"86","author":"Schelle","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.neuropharm.2017.08.031","article-title":"Chronic treatments with a 5-HT(4) receptor agonist decrease amyloid pathology in the entorhinal cortex and learning and memory deficits in the 5xFAD mouse model of Alzheimer\u2019s disease","volume":"126","author":"Baranger","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuropharm.2016.04.008","article-title":"Morin reverses neuropathological and cognitive impairments in APPswe\/PS1dE9 mice by targeting multiple pathogenic mechanisms","volume":"108","author":"Du","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.neuropharm.2016.12.002","article-title":"Geniposide ameliorates cognitive deficits by attenuating the cholinergic defect and amyloidosis in middle-aged Alzheimer model mice","volume":"116","author":"Zhao","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.3233\/JAD-190484","article-title":"Treatment with scFv-h3D6 Prevented Neuronal Loss and Improved Spatial Memory in Young 3xTg-AD Mice by Reducing the Intracellular Amyloid-beta Burden","volume":"70","author":"Roda","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"255","DOI":"10.31083\/j.jin2002025","article-title":"The effects of Danggui-Shaoyao-San on neuronal degeneration and amyloidosis in mouse and its molecular mechanism for the treatment of Alzheimer\u2019s disease","volume":"20","author":"Yang","year":"2021","journal-title":"J. Integr. Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s11010-020-03852-1","article-title":"Berberine attenuates Abeta-induced neuronal damage through regulating miR-188\/NOS1 in Alzheimer\u2019s disease","volume":"474","author":"Chen","year":"2020","journal-title":"Mol. Cell Biochem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13195-021-00769-9","article-title":"Preservation of dendritic spine morphology and postsynaptic signaling markers after treatment with solid lipid curcumin particles in the 5xFAD mouse model of Alzheimer\u2019s amyloidosis","volume":"13","author":"Maiti","year":"2021","journal-title":"Alzheimers Res. Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"112957","DOI":"10.1016\/j.jep.2020.112957","article-title":"Shenzao jiannao oral liquid, an herbal formula, ameliorates cognitive impairments by rescuing neuronal death and triggering endogenous neurogenesis in AD-like mice induced by a combination of Abeta42 and scopolamine","volume":"259","author":"Xiao","year":"2020","journal-title":"J. Ethnopharmacol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/4\/1210\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:17:44Z","timestamp":1760134664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/4\/1210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,11]]},"references-count":83,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["molecules27041210"],"URL":"https:\/\/doi.org\/10.3390\/molecules27041210","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,11]]}}}