Acosta C, Anderson HD, Anderson CM (2017) Astrocyte dysfunction in Alzheimer disease. J Neurosci Res 95:2430–2447. https://doi.org/10.1002/JNR.24075

Alsadat AM, Nikbakht F, Hossein Nia H, Golab F, Khadem Y, Barati M, Vazifekhah S (2021) GSK-3β as a target for apigenin-induced neuroprotection against Aβ 25–35 in a rat model of Alzheimer’s disease. Neuropeptides 90:102200. https://doi.org/10.1016/J.NPEP.2021.102200

Alzheimer’s Disease International. (2022) 2022 Alzheimer’s disease facts and figures. Alzheimer’s Dement 18:700–789. https://doi.org/10.1002/alz.12638

Alzheimer’s Disease International. (2020) 2020 Alzheimer’s disease facts and figures. Alzheimer’s Dement 16:391–460. https://doi.org/10.1002/alz.12068

Alzheimer’s Association (2019) 2019 Alzheimer’s disease facts and figures. Alzheimer’s Dement 15:321–387. https://doi.org/10.1016/j.jalz.2019.01.010

Arévalo JC, Wu SH (2006) Neurotrophin signaling: Many exciting surprises! In: Cellular and Molecular Life Sciences. Springer, pp 1523–1537

Arredondo F, Echeverry C, Abin-Carriquiry J a, Blasina F, Antúnez K, Jones DP, Go Y-M, Liang Y-L, Dajas F (2010) After cellular internalization, quercetin causes Nrf2 nuclear translocation, increases glutathione levels, and prevents neuronal death against an oxidative insult. Free Radic Biol Med 49:738–47. https://doi.org/10.1016/j.freeradbiomed.2010.05.020

Baki A, Bielik A, Molnár L, Szendrei G, Keserü GM (2007) A high throughput luminescent assay for glycogen synthase kinase-3β inhibitors. Assay Drug Dev Technol 5:75–83. https://doi.org/10.1089/adt.2006.029

Barbier P, Zejneli O, Martinho M, Lasorsa A, Belle V, Smet-Nocca C, Tsvetkov PO, Devred F, Landrieu I (2019) Role of tau as a microtubule-associated protein: Structural and functional aspects. Front Aging Neurosci 10:204. https://doi.org/10.3389/fnagi.2019.00204

Barceló S, Peralta M, Calise M, Finck S, Ortega G, Diez RA, Cabrera JL, Pérez C (2017) Interactions of a prenylated flavonoid from Dalea elegans with fluconazole against azole- resistant Candida albicans. Phytomedicine 15;32:24–29. https://doi.org/10.1016/j.phymed.2017.05.001

Belfiore R, Rodin A, Ferreira E, Velazquez R, Branca C, Caccamo A, Oddo S (2019) Temporal and regional progression of Alzheimer’s disease-like pathology in 3xTg‐AD mice. Aging Cell 18:. https://doi.org/10.1111/ACEL.12873

Boots AW, Kubben N, Haenen GRMM, Bast A (2003) Oxidized quercetin reacts with thiols rather than with ascorbate: Implication for quercetin supplementation. Biochem Biophys Res Commun 308:560–565. https://doi.org/10.1016/S0006-291X(03)01438-4

Bullock R (2006) Efficacy and safety of memantine in moderate-to-severe Alzheimer disease: The evidence to date. Alzheimer Dis Assoc Disord 20:23–29. https://doi.org/10.1097/01.WAD.0000201847.29836.A5

Carroll JC, Rosario ER, Kreimer S, Villamagna A, Gentzschein E, Stanczyk FZ, Pike CJ (2010) Sex differences in β-amyloid accumulation in 3xTg-AD mice: Role of neonatal sex steroid hormone exposure. Brain Res 1366:233–245. https://doi.org/10.1016/J.BRAINRES.2010.10.009

Carvalho D, Diaz-Amarilla P, Dapueto R, Santi MD, Duarte P, Savio E, Engler H, Abin-Carriquiry JA, Arredondo F (2023) Transcriptomic Analyses of Neurotoxic Astrocytes Derived from Adult Triple Transgenic Alzheimer’s Disease Mice. J Mol Neurosci 2023 1–29. https://doi.org/10.1007/S12031-023-02105-2

Clarke LE, Liddelow SA, Chakraborty C, Münch AE, Heiman M, Barres BA (2018) Normal aging induces A1-like astrocyte reactivity. Proc Natl Acad Sci U S A 115:E1896–E1905. https://doi.org/10.1073/pnas.1800165115

Clinton LK, Billings LM, Green KN, Caccamo A, Ngo J, Oddo S, McGaugh JL, LaFerla FM (2007) Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice. Neurobiol Dis 28:76–82. https://doi.org/10.1016/J.NBD.2007.06.013

Cragnolini AB, Friedman WJ (2008) The function of p75NTR in glia. Trends Neurosci 31:99–104. https://doi.org/10.1016/J.TINS.2007.11.005

Cummings J, Lee G, Zhong K, Fonseca J, Taghva K (2021) Alzheimer’s disease drug development pipeline: 2021. Alzheimer’s Dement Transl Res Clin Interv 7:e12179. https://doi.org/10.1002/TRC2.12179

Denizot F, Lang R (1986) Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 89:. https://doi.org/10.1016/0022-1759(86)90368-6

Di Muzio E, Toti D, Polticelli F (2017) DockingApp: a user friendly interface for facilitated docking simulations with AutoDock Vina. J Comput Aided Mol Des 31:213–218. https://doi.org/10.1007/s10822-016-0006-1

Diaz-Amarilla P, Arredondo F, Dapueto R, Boix V, Carvalho D, Santi MD, Vasilskis E, Mesquita-Ribeiro R, Dajas-Bailador F, Abin-Carriquiry JA, Engler H, Savio E (2022) Isolation and characterization of neurotoxic astrocytes derived from old triple transgenic Alzheimer’s disease mice. Neurochem Int 159:. https://doi.org/10.1016/j.neuint.2022.105403

Díaz-Amarilla P, Olivera-Bravo S, Trias E, Cragnolini A, Martínez-Palma L, Cassina P, Beckman J, Barbeito L (2011) Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 108:18126–18131. https://doi.org/10.1073/pnas.1110689108

Echeverry C, Arredondo F, Abin-Carriquiry JA, Midiwo JO, Ochieng C, Kerubo L, Dajas F (2010) Pretreatment with natural flavones and neuronal cell survival after oxidative stress: a structure-activity relationship study. J Agric Food Chem 58:2111–5. https://doi.org/10.1021/jf902951v

Escartin C, Galea E, Lakatos A, O’Callaghan JP, Petzold GC, Serrano-Pozo A, Steinhäuser C, Volterra A, Carmignoto G, Agarwal A, Allen NJ, Araque A, Barbeito L, Barzilai A, Bergles DE, Bonvento G, Butt AM, Chen WT, Cohen-Salmon M, et al (2021) Reactive astrocyte nomenclature, definitions, and future directions. Nat. Neurosci. 24:312–325

Fahnestock M, Shekari A (2019) ProNGF and neurodegeneration in Alzheimer’s disease. Front. Neurosci. 13:129

Fährrolfes R, Bietz S, Flachsenberg F, Meyder A, Nittinger E, Otto T, Volkamer A, Rarey M (2017) Proteins Plus: A web portal for structure analysis of macromolecules. Nucleic Acids Res 45:W337–W343. https://doi.org/10.1093/nar/gkx333

Gong EJ, Park HR, Kim ME, Piao S, Lee E, Jo DG, Chung HY, Ha NC, Mattson MP, Lee J (2011) Morin attenuates tau hyperphosphorylation by inhibiting GSK3β. Neurobiol Dis 44:223–230. https://doi.org/10.1016/J.NBD.2011.07.005

Heneka MT, Carson MJ, Khoury J El, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, Herrup K, Frautschy SA, Finsen B, Brown GC, Verkhratsky A, Yamanaka K, Koistinaho J, Latz E, Halle A, et al (2015) Neuroinflammation in Alzheimer’s Disease. Lancet Neurol 14:388. https://doi.org/10.1016/S1474-4422(15)70016-5

Hernandez F, Lucas JJ, Avila J (2013) GSK3 and tau: two convergence points in Alzheimer’s disease. J Alzheimers Dis 33 Suppl 1: https://doi.org/10.3233/JAD-2012-129025

Hirokawa N, Funakoshi T, Sato-Harada R, Kanai Y (1996) Selective stabilization of tau in axons and microtubule-associated protein 2 C in cell bodies and dendrites contributes to polarized localization of cytoskeletal proteins in mature neurons. J Cell Biol 132:667–679. https://doi.org/10.1083/JCB.132.4.667

Hole KL, Williams RJ (2020) Flavonoids as an Intervention for Alzheimer’s Disease: Progress and Hurdles Towards Defining a Mechanism of Action. Brain Plast 6:167–192. https://doi.org/10.3233/BPL-200098

Hooper C, Killick R, Lovestone S (2008) The GSK3 hypothesis of Alzheimer’s disease. 104:1433–1439. https://doi.org/10.1111/j.1471-4159.2007.05194.x

Humphrey W, Dalke A, Schulten K (1996) VMD: Visual molecular dynamics. J Mol Graph 14:33–38. https://doi.org/10.1016/0263-7855(96)00018-5

Iram T, Trudler D, Kain D, Kanner S, Galron R, Vassar R, Barzilai A, Blinder P, Fishelson Z, Frenkel D (2016) Astrocytes from old Alzheimer’s disease mice are impaired in Aβ uptake and in neuroprotection. Neurobiol Dis 96:84–94. https://doi.org/10.1016/j.nbd.2016.08.001

Jiang W, Luo T, Li S, Zhou Y, Shen XY, He F, Xu J, Wang HQ (2016) Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons. PLoS One 11:e0152371. https://doi.org/10.1371/JOURNAL.PONE.0152371

Jope RS, Mines MA, Beurel E (2011) Regulation of cell survival mechanisms in alzheimer’s disease by glycogen synthase kinase-3. Int J Alzheimers Dis. https://doi.org/10.4061/2011/861072

Kollman PA, Massova I, Reyes C, Kuhn B, Huo S, Chong L, Lee M, Lee T, Duan Y, Wang W, Donini O, Cieplak P, Srinivasan J, Case DA, Cheatham TE (2000) Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res 33:889–897. https://doi.org/10.1021/AR000033J

Kulijewicz-Nawrot M, Verkhratsky A, Chvátal A, Syková E, Rodríguez JJ (2012) Astrocytic cytoskeletal atrophy in the medial prefrontal cortex of a triple transgenic mouse model of Alzheimer’s disease. J Anat 221:252–262. https://doi.org/10.1111/J.1469-7580.2012.01536.X

Lee R, Kermani P, Teng KK, Hempstead BL (2001) Regulation of cell survival by secreted proneurotrophins. Science 294:1945–1948. https://doi.org/10.1126/SCIENCE.1065057

Li J, Sun M, Cui X, Li C (2022) Protective Effects of Flavonoids against Alzheimer’s Disease: Pathological Hypothesis, Potential Targets, and Structure–Activity Relationship. Int J Mol Sci 23:10020. https://doi.org/10.3390/ijms231710020

Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Münch AE, Chung W-SS, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Buckwalter MS, Rowitch DH, Dawson VL, Dawson TM, et al (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541:481–487. https://doi.org/10.1038/nature21029

Lima E, Rauter AP, Medeiros J (2023) Flavonoids as Promising Multitarget Agents in Alzheimer’s Disease Therapy. Appl Sci 2023, Vol 13, Page 4651 13:4651. https://doi.org/10.3390/APP13084651

Liu H, Hou T (2016) CaFE: a tool for binding affinity prediction using end-point free energy methods. Bioinformatics 32:2216–2218. https://doi.org/10.1093/BIOINFORMATICS/BTW215

Lynch C, Alzheimer’s Disease International. (2019) World Alzheimer Report 2019. Alzheimer’s Dement 16:e038255. https://doi.org/10.1002/alz.038255

Mahase E (2021a) Aducanumab: European agency rejects Alzheimer’s drug over efficacy and safety concerns. BMJ 375:n3127. https://doi.org/10.1136/BMJ.N3127

Mahase E (2021b) FDA approves controversial Alzheimer’s drug despite uncertainty over effectiveness. BMJ 373:. https://doi.org/10.1136/BMJ.N1462

Martínez-Busi M, Arredondo F, González D, Echeverry C, Vega-Teijido MA, Carvalho D, Rodríguez-Haralambides A, Rivera F, Dajas F, Abin-Carriquiry JA (2019) Purification, structural elucidation, antioxidant capacity and neuroprotective potential of the main polyphenolic compounds contained in Achyrocline satureioides (Lam) D.C. (Compositae). Bioorganic Med Chem 27:. https://doi.org/10.1016/j.bmc.2019.03.047

Mysona BA, Matragoon S, Stephens M, Mohamed IN, Farooq A, Bartasis ML, Fouda AY, Shanab AY, Espinosa-Heidmann DG, El-Remessy AB (2015) Imbalance of the nerve growth factor and its precursor as a potential biomarker for diabetic retinopathy. 2015:571456. https://doi.org/10.1155/2015/571456

Noble W, Olm V, Takata K, Casey E, Mary O, Meyerson J, Gaynor K, LaFrancois J, Wang L, Kondo T, Davies P, Burns M, Veeranna, Nixon R, Dickson D, Matsuoka Y, Ahlijanian M, Lau LF, Duff K (2003) Cdk5 Is a Key Factor in Tau Aggregation and Tangle Formation In Vivo. Neuron 38:555–565. https://doi.org/10.1016/S0896-6273(03)00259-9

Oddo S, Caccamo A, Kitazawa M, Tseng BP, LaFerla FM (2003) Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer’s disease. Neurobiol Aging 24:1063–1070. https://doi.org/10.1016/J.NEUROBIOLAGING.2003.08.012

Olabarria M, Noristani HN, Verkhratsky A, Rodríguez JJ (2010) Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer’s disease. Glia 58:831–838. https://doi.org/10.1002/GLIA.20967

Ossenkoppele R, Schonhaut DR, Schöll M, Lockhart SN, Ayakta N, Baker SL, O’Neil JP, Janabi M, Lazaris A, Cantwell A, Vogel J, Santos M, Miller ZA, Bettcher BM, Vossel KA, Kramer JH, Gorno-Tempini ML, Miller BL, Jagust WJ, et al (2016) Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease. Brain 139:1551–1567. https://doi.org/10.1093/BRAIN/AWW027

Peralta MA, Santi MD, Agnese AM, Cabrera JL, Ortega MG (2014) Flavanoids from Dalea elegans: Chemical reassignment and determination of kinetics parameters related to their anti-tyrosinase activity. Phytochem Lett 10:260–267. https://doi.org/10.1016/j.phytol.2014.10.012

Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera - A visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612. https://doi.org/10.1002/jcc.20084

Phillips JC, Hardy DJ, Maia JDC, Stone JE, Ribeiro J V., Bernardi RC, Buch R, Fiorin G, Hénin J, Jiang W, McGreevy R, Melo MCR, Radak BK, Skeel RD, Singharoy A, Wang Y, Roux B, Aksimentiev A, Luthey-Schulten Z, et al (2020) Scalable molecular dynamics on CPU and GPU architectures with NAMD. J Chem Phys 153:044130. https://doi.org/10.1063/5.0014475

Prince MJ, Wimo A, Guerchet MM, Ali GC, Wu Y-T, Prina M (2015) World Alzheimer Report 2015 - The Global Impact of Dementia. Alzheimer’s Disease International, London

Reitz C, Mayeux R (2014) Alzheimer disease: Epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem Pharmacol 88:640–651. https://doi.org/10.1016/j.bcp.2013.12.024

Ribeiro J V., Bernardi RC, Rudack T, Stone JE, Phillips JC, Freddolino PL, Schulten K (2016) QwikMD — Integrative Molecular Dynamics Toolkit for Novices and Experts. Sci Reports 2016 61 6:1–14. https://doi.org/10.1038/srep26536

Ritchie CW, Ames D, Clayton T, Lai R (2004) Metaanalysis of Randomized Trials of the Efficacy and Safety of Donepezil, Galantamine, and Rivastigmine for the Treatment of Alzheimer Disease. Am J Geriatr Psychiatry 12:358–369. https://doi.org/10.1097/00019442-200407000-00003

Salentin S, Schreiber S, Haupt VJ, Adasme MF, Schroeder M (2015) PLIP: Fully automated protein-ligand interaction profiler. Nucleic Acids Res 43:W443–W447. https://doi.org/10.1093/nar/gkv315

Santi MD, Arredondo F, Carvalho D, Echeverry C, Prunell G, Peralta MA, Cabrera JL, Ortega MG, Savio E, Abin-Carriquiry JA (2020) Neuroprotective effects of prenylated flavanones isolated from Dalea species, in vitro and in silico studies. Eur J Med Chem 206:112718. https://doi.org/10.1016/J.EJMECH.2020.112718

Santi MD, Peralta MA, Mendoza CS, Cabrera JL, Ortega MG (2017) Chemical and bioactivity of flavanones obtained from roots of Dalea pazensis Rusby. 27:1789–1794. https://doi.org/10.1016/j.bmcl.2017.02.058

Strang KH, Golde TE, Giasson BI (2019) MAPT mutations, tauopathy, and mechanisms of neurodegeneration. Lab Investig 2019 997 99:912–928. https://doi.org/10.1038/s41374-019-0197-x

Stutzmann GE (2007) The pathogenesis of Alzheimers disease is it a lifelong “calciumopathy”? Neuroscientist 13:546–559. https://doi.org/10.1177/1073858407299730

Thal DR, Vandenberghe R (2016) Monitoring the progression of Alzheimer’s disease with τ-PET. Brain 139:1318–1320. https://doi.org/10.1093/BRAIN/AWW057

Tiveron C, Fasulo L, Capsoni S, Malerba F, Marinelli S, Paoletti F, Piccinin S, Scardigli R, Amato G, Brandi R, Capelli P, D’Aguanno S, Florenzano F, La Regina F, Lecci A, Manca A, Meli G, Pistillo L, Berretta N, et al (2013) ProNGF\NGF imbalance triggers learning and memory deficits, neurodegeneration and spontaneous epileptic-like discharges in transgenic mice. Cell Death Differ 20:1017–1030. https://doi.org/10.1038/cdd.2013.22

van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer LD, Iwatsubo T (2022) Lecanemab in Early Alzheimer’s Disease. N Engl J Med. https://doi.org/10.1056/NEJMoa2212948

Visser PJ, Reus LM, Gobom J, Jansen I, Dicks E, van der Lee SJ, Tsolaki M, Verhey FRJ, Popp J, Martinez-Lage P, Vandenberghe R, Lleó A, Molinuevo JL, Engelborghs S, Freund-Levi Y, Froelich L, Sleegers K, Dobricic V, Lovestone S, et al (2022) Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer’s disease. Mol Neurodegener 17:. https://doi.org/10.1186/S13024-022-00521-3

Wang D, Liu L, Zhu X, Wu W, Wang Y (2014) Hesperidin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress in a mouse model of Alzheimer’s disease. Cell Mol Neurobiol 34:1209–1221. https://doi.org/10.1007/S10571-014-0098-X

Williams RJ, Mohanakumar KP, Beart PM (2021) Neuro-nutraceuticals: Natural products nourish the brain but be aware of contrary effects. Neurochem Int 150:105159. https://doi.org/10.1016/J.NEUINT.2021.105159

Yiannopoulou KG, Papageorgiou SG (2020) Current and Future Treatments in Alzheimer Disease: An Update. J Cent Nerv Syst Dis 12:1179573520907397. https://doi.org/10.1177/1179573520907397