Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, Brayne C, Burns A, Cohen-Mansfield J, Cooper C. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet. 2020;396:413–46.

Article  Google Scholar 

Yiannopoulou KG, Papageorgiou SG. Current and future treatments in Alzheimer disease: an update. J Central Nervous Syst Dis. 2020;12:1179573520907397.

Google Scholar 

Qiu C, Fratiglioni L. Aging without dementia is achievable: current evidence from epidemiological research. J Alzheimers Dis. 2018;62:933–42.

Article  PubMed  PubMed Central  Google Scholar 

Srivastava S, Ahmad R, Khare SK. Alzheimer’s disease and its treatment by different approaches: a review. Eur J Med Chem. 2021;216: 113320.

Article  CAS  PubMed  Google Scholar 

Zhao J, Liu X, Xia W, Zhang Y, Wang C. Targeting amyloidogenic processing of APP in Alzheimer’s disease. Front Mol Neurosci. 2020;13:137.

Article  CAS  PubMed  PubMed Central  Google Scholar 

De Falco A, Cukierman DS, Hauser-Davis RA, Rey NA. Alzheimer’s disease: etiological hypotheses and treatment perspectives. Quim Nova. 2016;39:63–80.

Google Scholar 

Selkoe DJ. Normal and abnormal biology of the beta-amyloid precursor protein. Annu Rev Neurosci. 1994;17:489–517.

Article  CAS  PubMed  Google Scholar 

O’brien RJ, Wong PC. Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci. 2011;34:185–204.

Article  PubMed  PubMed Central  Google Scholar 

Gu Z, Cao H, Zuo C, Huang Y, Miao J, Song Y, Yang Y, Zhu L, Wang F. TFEB in Alzheimer’s disease: from molecular mechanisms to therapeutic implications. Neurobiol Dis. 2022;173:105855.

Article  CAS  PubMed  Google Scholar 

Zhang Z, Yang X, Song Y-Q, Tu J. Autophagy in Alzheimer’s disease pathogenesis: therapeutic potential and future perspectives. Ageing Res Rev. 2021;72: 101464.

Article  CAS  PubMed  Google Scholar 

Kepchia D, Huang L, Dargusch R, Rissman RA, Shokhirev MN, Fischer W, Schubert D. Diverse proteins aggregate in mild cognitive impairment and Alzheimer’s disease brain. Alzheimer’s Res Ther. 2020;12:1–20.

Google Scholar 

Yu WH, Cuervo AM, Kumar A, Peterhoff CM, Schmidt SD, Lee J-H, Mohan PS, Mercken M, Farmery MR, Tjernberg LO. Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer’s disease. J Cell Biol. 2005;171:87–98.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Krishnan S, Shrestha Y, Jayatunga DP, Rea S, Martins R, Bharadwaj P. Activate or inhibit? Implications of autophagy modulation as a therapeutic strategy for Alzheimer’s disease. Int J Mol Sci. 2020;21:6739.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Son SM, Park SJ, Fernandez-Estevez M, Rubinsztein DC. Autophagy regulation by acetylation—implications for neurodegenerative diseases. Exp Mol Med. 2021;53:30–41.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wolfe DM, Lee Jh, Kumar A, Lee S, Orenstein SJ, Nixon RA. Autophagy failure in Alzheimer’s disease and the role of defective lysosomal acidification. Eur J Neurosci. 2013;37:1949–61.

Article  PubMed  PubMed Central  Google Scholar 

Heckmann BL, Teubner BJ, Boada-Romero E, Tummers B, Guy C, Fitzgerald P, Mayer U, Carding S, Zakharenko SS, Wileman T. Noncanonical function of an autophagy protein prevents spontaneous Alzheimer’s disease. Sci Adv. 2020;6:e9036.

Article  Google Scholar 

Pickford F, Masliah E, Britschgi M, Lucin K, Narasimhan R, Jaeger PA, Small S, Spencer B, Rockenstein E, Levine B. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid β accumulation in mice. J Clin Investig. 2008;118:2190–9.

CAS  PubMed  PubMed Central  Google Scholar 

Long Z, Chen J, Zhao Y, Zhou W, Yao Q, Wang Y, He G. Dynamic changes of autophagic flux induced by Abeta in the brain of postmortem Alzheimer’s disease patients, animal models and cell models. Aging (Albany NY). 2020;12:10912.

Article  CAS  PubMed  Google Scholar 

Heckmann BL, Teubner BJW, Tummers B, Boada-Romero E, Harris L, Yang M, Guy CS, Zakharenko SS, Green DR. LC3-associated endocytosis facilitates β-amyloid clearance and mitigates neurodegeneration in murine Alzheimer’s disease. Cell. 2019;178:536-551.e514.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bordi M, Berg MJ, Mohan PS, Peterhoff CM, Alldred MJ, Che S, Ginsberg SD, Nixon RA. Autophagy flux in CA1 neurons of Alzheimer hippocampus: increased induction overburdens failing lysosomes to propel neuritic dystrophy. Autophagy. 2016;12:2467–83.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen LQ, Wei JS, Lei ZN, Zhang LM, Liu Y, Sun FY. Induction of Bcl-2 and Bax was related to hyperphosphorylation of tau and neuronal death induced by okadaic acid in rat brain. Anatomical Record Part A Discoveries Mol Cell Evol Biol. 2005;287:1236–45.

Article  Google Scholar 

Rohn TT, Vyas V, Hernandez-Estrada T, Nichol KE, Christie L-A, Head E. Lack of pathology in a triple transgenic mouse model of Alzheimer’s disease after overexpression of the anti-apoptotic protein Bcl-2. J Neurosci. 2008;28:3051–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen Z, Gibson TB, Robinson F, Silvestro L, Pearson G, Xu B-E, Wright A, Vanderbilt C, Cobb MH. MAP kinases. Chem Rev. 2001;101:2449–76.

Article  CAS  PubMed  Google Scholar 

Zhang H, Wei W, Zhao M, Ma L, Jiang X, Pei H, Cao Y, Li H. Interaction between Aβ and tau in the pathogenesis of Alzheimer’s disease. Int J Biol Sci. 2021;17:2181.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Domise M, Didier S, Marinangeli C, Zhao H, Chandakkar P, Buée L, Viollet B, Davies P, Marambaud P, Vingtdeux V. AMP-activated protein kinase modulates tau phosphorylation and tau pathology in vivo. Sci Rep. 2016;6:1–12.

Article  Google Scholar 

Majeed Y, Halabi N, Madani AY, Engelke R, Bhagwat AM, Abdesselem H, Agha MV, Vakayil M, Courjaret R, Goswami N. SIRT1 promotes lipid metabolism and mitochondrial biogenesis in adipocytes and coordinates adipogenesis by targeting key enzymatic pathways. Sci Rep. 2021;11:8177.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shah S, Yoon G, Chung S, Abid M, Kim T, Lee H, Kim M. Novel osmotin inhibits SREBP2 via the AdipoR1/AMPK/SIRT1 pathway to improve Alzheimer’s disease neuropathological deficits. Mol Psychiatry. 2017;22:407–16.

Article  CAS  PubMed  Google Scholar 

Choi H, Park H-H, Lee K-Y, Choi N-Y, Yu H-J, Lee YJ, Park J, Huh Y-M, Lee S-H, Koh S-H. Coenzyme Q10 restores amyloid beta-inhibited proliferation of neural stem cells by activating the PI3K pathway. Stem Cells Dev. 2013;22:2112–20.

Article  CAS  PubMed  Google Scholar 

Choi H, Park H-H, Koh S-H, Choi N-Y, Yu H-J, Park J, Lee YJ, Lee K-Y. Coenzyme Q10 protects against amyloid beta-induced neuronal cell death by inhibiting oxidative stress and activating the P13K pathway. Neurotoxicology. 2012;33:85–90.

Article  CAS  PubMed  Google Scholar 

Sun Y, Wu A, Li X, Qin D, Jin B, Liu J, Tang Y, Wu J, Yu C. The seed of Litchi chinensis fraction ameliorates hippocampal neuronal injury in an Aβ25-35-induced Alzheimer’s disease rat model via the AKT/GSK-3β pathway. Pharm Biol. 2020;58:35–43.

Article  CAS  PubMed  Google Scholar 

Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991;30:572–80.

Article  CAS  PubMed  Google Scholar 

John A, Reddy PH. Synaptic basis of Alzheimer’s disease: focus on synaptic amyloid beta, P-tau and mitochondria. Ageing Res Rev. 2021;65: 101208.

Article  CAS  PubMed  Google Scholar 

Horner AE, Norris RH, McLaren-Jones R, Alexander L, Komiyama NH, Grant SG, Nithianantharajah J, Kopanitsa MV. Learning and reaction times in mouse touchscreen tests are differentially impacted by mutations in genes encoding postsynaptic interacting proteins SYNGAP1, NLGN3, DLGAP1, DLGAP2 and SHANK2. Genes Brain Behav. 2021;20: e12723.

Article  PubMed  Google Scholar 

Smith TD, Adams MM, Gallagher M, Morrison JH, Rapp PR. Circuit-specific alterations in hippocampal synaptophysin immunoreactivity predict spatial learning impairment in aged rats. J Neurosci. 2000;20:6587–93.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xia Z, Wang F, Zhou S, Zhang R, Wang F, Huang JH, Wu E, Zhang Y, Hu Y. Catalpol protects synaptic proteins from beta-amyloid induced neuron injury and improves cognitive functions in aged rats. Oncotarget. 2017;8:69303.

Article  PubMed  PubMed Central  Google Scholar 

Gylys KH, Fein JA, Yang F, Wiley DJ, Miller CA, Cole GM. Synaptic changes in Alzheimer’s disease: increased amyloid-β and gliosis in surviving terminals is accompanied by decreased PSD-95 fluorescence. Am J Pathol. 2004;165:1809–17.

Article  CAS