{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:29:02Z","timestamp":1787218142883,"version":"build-2736575974"},"reference-count":171,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) exhibits marked sex differences, with women bearing a disproportionate burden of disease, particularly after midlife. Among the major factors contributing to this vulnerability, the apolipoprotein E \u03f54 allele (APOE4) and the abrupt endocrine transition of perimenopause have emerged as two critical and potentially synergistic drivers of neurodegeneration. Microglia, the resident immune cells of the central nervous system, lie at the center of this interaction because they integrate genetic, hormonal, metabolic, and inflammatory signals that shape amyloid clearance, synaptic remodeling, and neuroimmune homeostasis. Accumulating evidence indicates that APOE4 impairs microglial phagocytosis, disrupts lipid handling and lysosomal function, promotes pro-inflammatory activation, and compromises neurovascular integrity. In parallel, estrogen normally restrains microglial inflammatory signaling and supports phagocytic, metabolic, and reparative functions through estrogen receptor-dependent pathways. During perimenopause, fluctuating estrogen deficiency removes these protective constraints, thereby increasing the susceptibility of microglia to APOE4-driven dysfunction. This review synthesizes current evidence supporting an integrated pathogenic framework centered on the \u201cAPOE4-estrogen deficiency-microglia axis.\u201d We discuss how this axis promotes chronic neuroinflammation, synaptotoxicity, amyloid and tau pathology, mitochondrial dysfunction, blood\u2013brain barrier disruption, and large-scale network disconnection, ultimately accelerating cognitive decline in women. We also summarize relevant experimental models, including APOE-targeted murine paradigms, ovariectomy and accelerated ovarian failure models, human induced pluripotent stem cell-derived microglia, and emerging single-cell and spatial omics approaches. Finally, we highlight translational opportunities, including precision hormone-based interventions, selective estrogen receptor modulation, TREM2-centered microglial therapies, APOE4-directed molecular and genetic strategies, and biomarker-guided multi-target interventions during the perimenopausal \u201cwindow of opportunity.\u201d By integrating molecular mechanisms with translational perspectives, this review proposes a precision medicine framework for preventing or delaying neurodegenerative progression in high-risk perimenopausal women.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1925850","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:21:18Z","timestamp":1787217678000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The APOE4-estrogen-microglia axis in perimenopausal cognitive changes: mechanisms and therapeutic implications"],"prefix":"10.3389","volume":"17","author":[{"given":"Liuqing","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Acupuncture and Moxibustion, Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuntong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Acupuncture and Moxibustion, Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Acupuncture and Moxibustion, Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Acupuncture and Moxibustion, Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Acupuncture and Moxibustion, Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjing","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Acupuncture and Moxibustion, Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Feng","sequence":"additional","affiliation":[{"name":"Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Acupuncture and Moxibustion, Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Acupuncture and Moxibustion, Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Ren","sequence":"additional","affiliation":[{"name":"Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00430","article-title":"Amyloid beta and microRNAs in Alzheimer's disease","volume":"13","author":"Amakiri","year":"2019","journal-title":"Front Neurosci"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.332127","article-title":"Amyloid-beta peptide and tau protein crosstalk in Alzheimer's disease","volume":"17","author":"Roda","year":"2022","journal-title":"Neural Regener Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.brainres.2019.05.031","article-title":"Sex differences in Alzheimer's disease: understanding the molecular impact","volume":"1719","author":"Toro","year":"2019","journal-title":"Brain Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2023.01.001","article-title":"Sex differences in Alzheimer's disease","volume":"41","author":"Aggarwal","year":"2023","journal-title":"Neurol Clin"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.31448","article-title":"Association of premenopausal bilateral oophorectomy with cognitive performance and risk of mild cognitive impairment","volume":"4","author":"Rocca","year":"2021","journal-title":"JAMA Netw Open"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1210\/clinem\/dgaa764","article-title":"The menopause transition: signs, symptoms, and management options","volume":"106","author":"Santoro","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1080\/13697137.2021.1892627","article-title":"Menopause and cognitive complaints: are ovarian hormones linked with subjective cognitive decline","volume":"24","author":"Reuben","year":"2021","journal-title":"Climacteric"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1202-06.2006","article-title":"Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation","volume":"26","author":"Oakley","year":"2006","journal-title":"J Neurosci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180678","article-title":"5xFAD mice display sex-dependent inflammatory gene induction during the prodromal stage of Alzheimer's disease","volume":"70","author":"Manji","year":"2019","journal-title":"J Alzheimers Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210523","article-title":"Sex differences in behavior and molecular pathology in the 5XFAD model","volume":"85","author":"Sil","year":"2022","journal-title":"J Alzheimers Dis"},{"key":"B11","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/S1474-4422(20)30412-9","article-title":"APOE and Alzheimer's disease: advances in genetics, pathophysiology, and therapeutic approaches","volume":"20","author":"Serrano-Pozo","year":"2021","journal-title":"Lancet Neurol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-020-00218-z","article-title":"CRISPR-Cas9: a promising genome editing therapeutic tool for Alzheimer's disease-a narrative review","volume":"9","author":"Barman","year":"2020","journal-title":"Neurol Ther"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2417515122","article-title":"Suppressing APOE4-induced neural pathologies by targeting the VHL-HIF axis","volume":"122","author":"Jiang","year":"2025","journal-title":"Proc Natl Acad Sci USA"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2023.09.004","article-title":"The cell biology of APOE in the brain","volume":"34","author":"Windham","year":"2024","journal-title":"Trends Cell Biol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16344","article-title":"Lipid metabolism and Alzheimer's disease: clinical evidence, mechanistic link and therapeutic promise","volume":"290","author":"Yin","year":"2023","journal-title":"FEBS J"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1177\/13872877251360321","article-title":"From APOE to cellular changes: unraveling the multidimensional mechanisms of blood-brain barrier damage in Alzheimer's disease","volume":"107","author":"Jiang","year":"2025","journal-title":"J Alzheimers Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01640-9","article-title":"Cell-autonomous effects of APOE4 in restricting microglial response in brain homeostasis and Alzheimer's disease","volume":"24","author":"Liu","year":"2023","journal-title":"Nat Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.16360","article-title":"Estrogen signalling and Alzheimer's disease: decoding molecular mechanisms for therapeutic breakthrough","volume":"60","author":"Rishabh","year":"2024","journal-title":"Eur J Neurosci"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151948","article-title":"TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques","volume":"213","author":"Wang","year":"2016","journal-title":"J Exp Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nature24016","article-title":"ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy","volume":"549","author":"Shi","year":"2017","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00256","article-title":"Transcriptome analyses in BV2 microglial cells following treatment with amino-terminal fragments of apolipoprotein E","volume":"12","author":"Pollock","year":"2020","journal-title":"Front Aging Neurosci"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1016\/j.celrep.2019.03.099","article-title":"The major risk factors for Alzheimer's disease: age, sex, and genes modulate the microglia response to A\u03b2 plaques","volume":"27","author":"Sala Frigerio","year":"2019","journal-title":"Cell Rep"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02987-4","article-title":"Identification of female-enriched and disease-associated microglia (FDAMic) contributes to sexual dimorphism in late-onset Alzheimer's disease","volume":"21","author":"Wu","year":"2024","journal-title":"J Neuroinflamm"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25158485","article-title":"Sex and gender differences in Alzheimer's disease: genetic, hormonal, and inflammation impacts","volume":"25","author":"Kolahchi","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003955","article-title":"Reproductive factors and the risk of incident dementia: a cohort study of UK Biobank participants","volume":"19","author":"Gong","year":"2022","journal-title":"PloS Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.102033","article-title":"Association of earlier age at menopause with risk of incident dementia, brain structural indices and the potential mediators: a prospective community-based cohort study","volume":"60","author":"Liao","year":"2023","journal-title":"EClinicalMedicine"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2018.34","article-title":"Female sex and Alzheimer's risk: the menopause connection","volume":"5","author":"Scheyer","year":"2018","journal-title":"J Prev Alzheimers Dis"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2025.1578439","article-title":"From hormones to neurodegeneration: how FSH drives Alzheimer's disease","volume":"17","author":"Xue","year":"2025","journal-title":"Front Aging Neurosci"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2024.109941","article-title":"NLRP3 inflammasome signalling in Alzheimer's disease","volume":"252","author":"McManus","year":"2024","journal-title":"Neuropharmacology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.yfrne.2013.08.001","article-title":"Estrogen: a master regulator of bioenergetic systems in the brain and body","volume":"35","author":"Rettberg","year":"2014","journal-title":"Front Neuroendocrinol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.121146898","article-title":"Tracking the estrogen receptor in neurons: implications for estrogen-induced synapse formation","volume":"98","author":"McEwen","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00312","article-title":"Inflammation: bridging age, menopause and APOE\u03f54 genotype to Alzheimer's disease","volume":"10","author":"Mishra","year":"2018","journal-title":"Front Aging Neurosci"},{"key":"B33","doi-asserted-by":"publisher","first-page":"11546","DOI":"10.1038\/s41467-025-66726-4","article-title":"Perimenopausal state oestradiol to progesterone imbalance drives Alzheimer's risk via ERR\u03b1 dysregulation and energy dyshomeostasis","volume":"16","author":"Sun","year":"2025","journal-title":"Nat Commun"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2026.150226","article-title":"Harnessing estrogen's neuroprotective potential in mitigating Alzheimer's pathologies in postmenopausal women: a review","volume":"1879","author":"Manasa","year":"2026","journal-title":"Brain Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-021-06792-1","article-title":"Estrogenic hormones receptors in Alzheimer's disease","volume":"48","author":"Tecalco-Cruz","year":"2021","journal-title":"Mol Biol Rep"},{"key":"B36","doi-asserted-by":"publisher","first-page":"29","DOI":"10.2174\/1567205017666200212155234","article-title":"Microglia in alzheimer's disease","volume":"17","author":"S\u00fc\u00df","year":"2020","journal-title":"Curr Alzheimer Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-025-00711-w","article-title":"ER\u03b2 mediates sex-specific protection in the App-NL-G-F mouse model of Alzheimer's disease","volume":"16","author":"Demetriou","year":"2025","journal-title":"Biol Sex Differ"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-01911-8","article-title":"Estrogen signaling in Alzheimer's disease: molecular insights and therapeutic targets for Alzheimer's dementia","volume":"57","author":"Uddin","year":"2020","journal-title":"Mol Neurobiol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.896852","article-title":"Functional and phenotypic diversity of microglia: implication for microglia-based therapies for Alzheimer's disease","volume":"14","author":"Xu","year":"2022","journal-title":"Front Aging Neurosci"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20200162","article-title":"Estrogen receptors and the aging brain","volume":"65","author":"Maioli","year":"2021","journal-title":"Essays Biochem"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232112990","article-title":"Microglia and alzheimer's disease","volume":"23","author":"Merighi","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci15070675","article-title":"The APOE-microglia axis in Alzheimer's disease: functional divergence and therapeutic perspectives-a narrative review","volume":"15","author":"Liu","year":"2025","journal-title":"Brain Sci"},{"key":"B43","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s12974-026-03728-z","article-title":"Microglia TFEB activation attenuates Alzheimer's disease pathology by enhancing autophagy-lysosomal function","volume":"23","author":"Kim","year":"2026","journal-title":"J Neuroinflamm"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14219","article-title":"Degradation of NLRP3 by p62-dependent-autophagy improves cognitive function in Alzheimer's disease by maintaining the phagocytic function of microglia","volume":"29","author":"Zhang","year":"2023","journal-title":"CNS Neurosci Ther"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107530","article-title":"IL-33-PU.1 transcriptome reprogramming drives functional state transition and clearance activity of microglia in Alzheimer's disease","volume":"31","author":"Lau","year":"2020","journal-title":"Cell Rep"},{"key":"B46","doi-asserted-by":"publisher","first-page":"5370","DOI":"10.1038\/s41467-020-19227-5","article-title":"Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer's disease","volume":"11","author":"McQuade","year":"2020","journal-title":"Nat Commun"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2026.02.005","article-title":"MS4A4A and MS4A6A: new targets to enhance microglia protective function in Alzheimer's disease","volume":"114","author":"Hansen","year":"2026","journal-title":"Neuron"},{"key":"B48","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s13024-025-00887-0","article-title":"MS4A6A\/Ms4a6d deficiency disrupts neuroprotective microglia functions and promotes inflammation in Alzheimer's disease model","volume":"20","author":"Jiao","year":"2025","journal-title":"Mol Neurodegener"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.2174\/0113816128464813260512100753","article-title":"Extracellular vesicles in Alzheimer's disease: mechanisms, immunotherapy links, and clinical translation","author":"Kishor","year":"2026","journal-title":"Curr Pharm Des"},{"key":"B50","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s12916-019-1299-4","article-title":"ApoE4: an emerging therapeutic target for Alzheimer's disease","volume":"17","author":"Safieh","year":"2019","journal-title":"BMC Med"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2025.1464","article-title":"Dysregulated lipid metabolism and neurovascular unit dysfunction: Novel mechanisms linking Alzheimer's disease and vascular dementia","author":"Li","year":"2026","journal-title":"Aging Dis"},{"key":"B52","doi-asserted-by":"publisher","first-page":"139","DOI":"10.3892\/ijmm.2025.5580","article-title":"Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review)","volume":"56","author":"Sun","year":"2025","journal-title":"Int J Mol Med"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3390\/biom15111629","article-title":"Microglia-mediated phagocytosis in Alzheimer's disease: Mechanisms, heterogeneity, and therapeutic insights","volume":"15","author":"Hassan","year":"2025","journal-title":"Biomolecules"},{"key":"B54","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s00011-025-02016-5","article-title":"APOE4 impairs autophagy and A\u03b2 clearance by microglial cells","volume":"74","author":"Bassal","year":"2025","journal-title":"Inflammation Res"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24465","article-title":"How brain 'cleaners' fail: Mechanisms and therapeutic value of microglial phagocytosis in Alzheimer's disease","volume":"72","author":"Ni","year":"2024","journal-title":"Glia"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102649","article-title":"APOE4, Alzheimer's and periodontal disease: A scoping review","volume":"105","author":"Ar\u00e9valo-Caro","year":"2025","journal-title":"Ageing Res Rev"},{"key":"B57","doi-asserted-by":"publisher","first-page":"19471","DOI":"10.1038\/s41598-022-21920-y","article-title":"Naturally-aged microglia exhibit phagocytic dysfunction accompanied by gene expression changes reflective of underlying neurologic disease","volume":"12","author":"Thomas","year":"2022","journal-title":"Sci Rep"},{"key":"B58","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1007\/s12017-025-08898-2","article-title":"Targeting microglial activation to modulate neuroinflammation in Alzheimer's disease","volume":"27","author":"Patil","year":"2025","journal-title":"Neuromolecular Med"},{"key":"B59","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s11011-025-01631-9","article-title":"Microglial activation as a hallmark of neuroinflammation in Alzheimer's disease","volume":"40","author":"Ebrahimi","year":"2025","journal-title":"Metab Brain Dis"},{"key":"B60","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1007\/s11011-025-01739-y","article-title":"Rewiring brain immunity: Targeting microglial metabolism for neuroprotection in neurodegenerative disorders","volume":"40","author":"Shokr","year":"2025","journal-title":"Metab Brain Dis"},{"key":"B61","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1002\/JLB.3MR1021-531R","article-title":"Microglial activation in Alzheimer's disease: The role of flavonoids and microRNAs","volume":"112","author":"Medrano-Jim\u00e9nez","year":"2022","journal-title":"J Leukoc Biol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s40035-024-00445-6","article-title":"TRPV1 alleviates APOE4-dependent microglial antigen presentation and T cell infiltration in Alzheimer's disease","volume":"13","author":"Lu","year":"2024","journal-title":"Transl Neurodegener"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/5123565","article-title":"A fragment of apolipoprotein E4 leads to the downregulation of a CXorf56 homologue, a novel ER-associated protein, and activation of BV2 microglial cells","volume":"2019","author":"Pollock","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0295320","article-title":"Associations of serum DNA methylation levels of chemokine signaling pathway genes with mild cognitive impairment (MCI) and Alzheimer's disease (AD)","volume":"18","author":"Zou","year":"2023","journal-title":"PloS One"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.631827","article-title":"Interplay between microglia and Alzheimer's disease-focus on the most relevant risks: APOE genotype, sex and age","volume":"13","author":"Chen","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-026-02099-0","article-title":"Impact of sex differences on microglial function in Alzheimer's disease","author":"Figueiredo","year":"2026","journal-title":"Alzheimers Res Ther"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.2147\/ITT.S305420","article-title":"The role of complement in synaptic pruning and neurodegeneration","volume":"10","author":"Gomez-Arboledas","year":"2021","journal-title":"Immunotargets Ther"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1002\/alz.71185","article-title":"Spatial heterogeneity in microglia-complement crosstalk: Implications for synaptic pruning in Alzheimer's disease","volume":"22","author":"Ye","year":"2026","journal-title":"Alzheimers Dement"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-025-01740-4","article-title":"Synaptic pruning genes networks in Alzheimer's disease: Correlations with neuropathology and cognitive decline","volume":"48","author":"Sanfilippo","year":"2026","journal-title":"Geroscience"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03574-1","article-title":"Microglial mechanisms drive amyloid-\u03b2 clearance in immunized patients with Alzheimer's disease","volume":"31","author":"van Olst","year":"2025","journal-title":"Nat Med"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202412184","article-title":"Microglial Lyzl4 facilitates \u03b2-amyloid clearance in Alzheimer's disease","volume":"12","author":"Pan","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"B72","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1186\/s12974-021-02211-1","article-title":"Interleukin-10 deficiency exacerbates inflammation-induced tau pathology","volume":"18","author":"Weston","year":"2021","journal-title":"J Neuroinflamm"},{"key":"B73","doi-asserted-by":"publisher","first-page":"6577","DOI":"10.1038\/s41467-023-42282-7","article-title":"FSH and ApoE4 contribute to Alzheimer's disease-like pathogenesis via C\/EBP\u03b2\/\u03b4-secretase in female mice","volume":"14","author":"Xiong","year":"2023","journal-title":"Nat Commun"},{"key":"B74","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s40478-022-01404-w","article-title":"Terminal complement pathway activation drives synaptic loss in Alzheimer's disease models","volume":"10","author":"Carpanini","year":"2022","journal-title":"Acta Neuropathol Commun"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13682","article-title":"C5aR1 signaling promotes region- and age-dependent synaptic pruning in models of Alzheimer's disease","volume":"20","author":"Gomez-Arboledas","year":"2024","journal-title":"Alzheimers Dement."},{"key":"B76","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/s11596-026-00175-y","article-title":"PAR-1 in Alzheimer's disease: Pathophysiological insights and mechanistic perspectives","volume":"46","author":"Neha","year":"2026","journal-title":"Curr Med Sci"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-220359","article-title":"Sex differences in resilience and resistance to brain pathology and dysfunction moderated by cerebrovascular response to exercise and genetic risk for Alzheimer's disease","volume":"90","author":"Palmer","year":"2022","journal-title":"J Alzheimers Dis"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2025.1632877","article-title":"Accelerated midlife endocrine and bioenergetic brain aging in APOE4 females","volume":"17","author":"Wang","year":"2025","journal-title":"Front Aging Neurosci"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202523511","article-title":"Alzheimer's disease risk factor APOE4 exerts dimorphic effects on female bone","volume":"13","author":"Schurman","year":"2026","journal-title":"Adv Sci (Weinh)"},{"key":"B80","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1111\/joim.70036","article-title":"Bioenergetics and lipid metabolism in Alzheimer's disease: From cell biology to systemic health","volume":"299","author":"Maioli","year":"2026","journal-title":"J Intern Med"},{"key":"B81","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.bbi.2025.04.032","article-title":"SOAT1 dysregulation in astrocytes drives blood-brain barrier dysfunction and neuroinflammation in Alzheimer's disease","volume":"128","author":"Huang","year":"2025","journal-title":"Brain Behav Immun"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav6221","article-title":"Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer's disease","volume":"11","author":"Ewers","year":"2019","journal-title":"Sci Transl Med"},{"key":"B83","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13024-020-00407-2","article-title":"Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration","volume":"15","author":"Franzmeier","year":"2020","journal-title":"Mol Neurodegener"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR-D-24-01287","article-title":"Blood serum from individuals with Alzheimer's disease alters microglial phagocytosis in vitro","volume":"21","author":"Altendorfer","year":"2026","journal-title":"Neural Regener Res"},{"key":"B85","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1177\/13872877241313223","article-title":"Microglial polarization in Alzheimer's disease: Mechanisms, implications, and therapeutic opportunities","volume":"104","author":"Yang","year":"2025","journal-title":"J Alzheimers Dis"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12341","article-title":"Acute systemic inflammation exacerbates neuroinflammation in Alzheimer's disease: IL-1\u03b2 drives amplified responses in primed astrocytes and neuronal network dysfunction","volume":"17","author":"Lopez-Rodriguez","year":"2021","journal-title":"Alzheimers Dement"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.34133\/research.1163","article-title":"Porphyromonas gingivalis promotes neuroinflammation by microglial ferroptosis via NOX4\/PPAR-\u03b1\/PGC-1\u03b1 pathway","volume":"9","author":"Li","year":"2026","journal-title":"Res (Wash D C)"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12731","article-title":"Blood-based bioenergetic profiling reveals differences in mitochondrial function associated with cognitive performance and Alzheimer's disease","volume":"19","author":"Mahapatra","year":"2023","journal-title":"Alzheimers Dement"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-025-01776-6","article-title":"Nervonic acid and 15-epi-PGA1 mediate systemic mitochondrial dysfunction in AD dementia","volume":"48","author":"Heimler","year":"2026","journal-title":"Geroscience"},{"key":"B90","first-page":"2024.01.23.23297820","article-title":"Individual bioenergetic capacity as a potential source of resilience to Alzheimer's disease","volume-title":"Medrxiv","author":"Arnold","year":"2024"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci14050434","article-title":"Beneficial versus detrimental effects of complement-microglial interactions in Alzheimer's disease","volume":"14","author":"Ayyubova","year":"2024","journal-title":"Brain Sci"},{"key":"B92","doi-asserted-by":"publisher","first-page":"2030","DOI":"10.1038\/s41467-021-22301-1","article-title":"Loss of microglial SIRP\u03b1 promotes synaptic pruning in preclinical models of neurodegeneration","volume":"12","author":"Ding","year":"2021","journal-title":"Nat Commun"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.14055","article-title":"Drugs targeting APOE4 that regulate beta-amyloid aggregation in the brain: Therapeutic potential for Alzheimer's disease","volume":"135","author":"Poblano","year":"2024","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"B94","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.cell.2016.12.044","article-title":"ApoE2, ApoE3, and ApoE4 differentially stimulate APP transcription and A\u03b2 secretion","volume":"168","author":"Huang","year":"2017","journal-title":"Cell"},{"key":"B95","first-page":"2023.07.27.550884","article-title":"Enhanced microglial dynamics and paucity of tau seeding in the amyloid plaque microenvironment contributes to cognitive resilience in Alzheimer's disease","volume-title":"Biorxiv","author":"Jury-Garfe","year":"2023"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-025-05329-y","article-title":"The synergistic role of ApoE4 and GSK3\u03b2 in Alzheimer's disease: Pathological mechanisms and therapeutic implications","volume":"63","author":"Li","year":"2025","journal-title":"Mol Neurobiol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz026","article-title":"Functional connectivity associated with tau levels in ageing, Alzheimer's, and small vessel disease","volume":"142","author":"Franzmeier","year":"2019","journal-title":"Brain"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae211","article-title":"Association of glial fibrillary acid protein, Alzheimer's disease pathology and cognitive decline","volume":"147","author":"Peretti","year":"2024","journal-title":"Brain"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2247-3","article-title":"APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline","volume":"581","author":"Montagne","year":"2020","journal-title":"Nature"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-7643285\/v1","article-title":"Memory deficits in hypertensive ApoE4 mice reversed by P2Y12 inhibition via different mechanisms in males and perimenopausal females","author":"Trigiani","year":"2025","journal-title":"Res Sq"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.584135","article-title":"Vasculo-neuronal coupling and neurovascular coupling at the neurovascular unit: Impact of hypertension","volume":"11","author":"Presa","year":"2020","journal-title":"Front Physiol"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-021-00430-6","article-title":"Hypertension-induced cognitive impairment: From pathophysiology to public health","volume":"17","author":"Ungvari","year":"2021","journal-title":"Nat Rev Nephrol"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13057","article-title":"mTOR drives cerebrovascular, synaptic, and cognitive dysfunction in normative aging","volume":"19","author":"Van Skike","year":"2020","journal-title":"Aging Cell"},{"key":"B104","first-page":"2026.05.09.723490","article-title":"Alzheimer's disease risk allele APOE4 interacts with arsenic exposure to drive microglial dysfunction","volume-title":"Biorxiv","author":"Marchi","year":"2026"},{"key":"B105","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00401-024-02835-6","article-title":"Elevated expression of the retrotransposon LINE-1 drives Alzheimer's disease-associated microglial dysfunction","volume":"148","author":"Roy","year":"2024","journal-title":"Acta Neuropathol"},{"key":"B106","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.jpsychires.2021.09.029","article-title":"ApoE4 increases susceptibility to stress-induced age-dependent depression-like behavior and cognitive impairment","volume":"143","author":"Zhang","year":"2021","journal-title":"J Psychiatr Res"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.954980","article-title":"ApoE isoform-dependent effects of xanthohumol on high fat diet-induced cognitive impairments and hippocampal metabolic pathways","volume":"13","author":"Kundu","year":"2022","journal-title":"Front Pharmacol"},{"key":"B108","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s12964-025-02093-3","article-title":"ApoE2 affects insulin signaling in the hippocampus and spatial cognition of aged mice in a sex-dependent manner","volume":"23","author":"Wang","year":"2025","journal-title":"Cell Commun Signal"},{"key":"B109","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s13024-019-0352-2","article-title":"Synergistic effects of APOE and sex on the gut microbiome of young EFAD transgenic mice","volume":"14","author":"Maldonado Weng","year":"2019","journal-title":"Mol Neurodegener"},{"key":"B110","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.neurobiolaging.2021.02.020","article-title":"Age, sex, and cerebral microbleeds in EFAD Alzheimer disease mice","volume":"103","author":"Cacciottolo","year":"2021","journal-title":"Neurobiol Aging"},{"key":"B111","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1186\/s13195-023-01353-z","article-title":"A novel apoE-mimetic increases brain apoE levels, reduces A\u03b2 pathology and improves memory when treated before onset of pathology in male mice that express APOE3","volume":"15","author":"Valencia-Olvera","year":"2023","journal-title":"Alzheimers Res Ther"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.3233\/ADR-230053","article-title":"The effect of FTY720 on sphingolipid imbalance and cognitive decline in aged EFAD mice","volume":"8","author":"Luo","year":"2024","journal-title":"J Alzheimers Dis Rep"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00240","article-title":"Estradiol replacement at the critical period protects hippocampal neural stem cells to improve cognition in APP\/PS1 mice","volume":"12","author":"Qin","year":"2020","journal-title":"Front Aging Neurosci"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154056","article-title":"Biochanin A alleviates cognitive impairment and hippocampal mitochondrial damage in ovariectomized APP\/PS1 mice","volume":"100","author":"Hou","year":"2022","journal-title":"Phytomedicine"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14463","article-title":"Accelerated ovarian failure results in brain alterations related to Alzheimer's disease that are not recovered by high-intensity interval training in mice","volume":"21","author":"Mohammad","year":"2025","journal-title":"Alzheimers Dement"},{"key":"B116","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s12974-022-02459-1","article-title":"Synthetic amyloid beta does not induce a robust transcriptional response in innate immune cell culture systems","volume":"19","author":"Quiroga","year":"2022","journal-title":"J Neuroinflamm"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2024.103990","article-title":"Microglia-like cells from patient monocytes demonstrate increased phagocytic activity in probable Alzheimer's disease","volume":"132","author":"Gonul","year":"2025","journal-title":"Mol Cell Neurosci"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1111\/acel.70341","article-title":"Comparing functional consequences of human iPSC-microglia and neural stem cell-derived extracellular vesicles in mitigating cognitive decline in Alzheimer's disease","volume":"25","author":"Krattli","year":"2026","journal-title":"Aging Cell"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2020.101968","article-title":"Generation of a human induced pluripotent stem cell line (UEFi003-A) carrying heterozygous A673T variant in amyloid precursor protein associated with a reduced risk of Alzheimer's disease","volume":"48","author":"Rolova","year":"2020","journal-title":"Stem Cell Res"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2020.101979","article-title":"Generation and characterization of a novel human iPSC line from a resilient Alzheimer's disease patient","volume":"48","author":"Das","year":"2020","journal-title":"Stem Cell Res"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2025.0409","article-title":"Layer-specific colocalization of microglia with amyloid plaques in the middle temporal gyrus predicts cognitive decline in Alzheimer's disease","volume":"17","author":"Escari\u00e3o","year":"2025","journal-title":"Aging Dis"},{"key":"B122","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s12017-025-08844-2","article-title":"SP3-mediated transcriptional activation of GRIK1 is involved in Alzheimer's disease-induced cognitive decline by inducing inflammasome activation in microglia","volume":"27","author":"Pang","year":"2025","journal-title":"Neuromolecular Med"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2024.10.002","article-title":"Approaches for studying neuroimmune interactions in Alzheimer's disease","volume":"45","author":"Lin","year":"2024","journal-title":"Trends Immunol"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.50333","article-title":"Mechanisms of hyperexcitability in Alzheimer's disease hiPSC-derived neurons and cerebral organoids vs isogenic controls","volume":"8","author":"Ghatak","year":"2019","journal-title":"Elife"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102256","article-title":"Aging phenotype in AD brain organoids: Track to success and challenges","volume":"96","author":"Hossain","year":"2024","journal-title":"Ageing Res Rev"},{"key":"B126","first-page":"2025.06.04.653670","article-title":"Early neuronal reprogramming and cell cycle reentry shape Alzheimer's disease progression","volume-title":"Biorxiv","author":"Meir","year":"2025"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-025-04997-0","article-title":"Decoding Alzheimer's disease: Single-cell sequencing uncovers brain cell heterogeneity and pathogenesis","volume":"62","author":"Ma","year":"2025","journal-title":"Mol Neurobiol"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-022-01136-5","article-title":"Cell type-specific changes identified by single-cell transcriptomics in Alzheimer's disease","volume":"14","author":"Luquez","year":"2022","journal-title":"Genome Med"},{"key":"B129","first-page":"2024.11.18.24317499","article-title":"Integrating spatial transcriptomics and snRNA-seq data enhances differential gene expression analysis results of AD-related phenotypes","volume-title":"Medrxiv","author":"Tang","year":"2024"},{"key":"B130","first-page":"2024.04.18.590160","article-title":"Proteome profiling of cerebrospinal fluid using machine learning shows a unique protein signature associated with APOE4 genotype","volume-title":"Biorxiv","author":"Shvetcov","year":"2024"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2024.1515981","article-title":"Unraveling Alzheimer's disease: Insights from single-cell sequencing and spatial transcriptomic","volume":"15","author":"He","year":"2024","journal-title":"Front Neurol"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-73474-6","article-title":"Dual platform spatial transcriptomics reveals parvalbumin interneuron subtype vulnerability in mouse models of Alzheimer's disease","author":"Seo","year":"2026","journal-title":"Nat Commun"},{"key":"B133","doi-asserted-by":"publisher","first-page":"8170","DOI":"10.1038\/s41467-025-63328-y","article-title":"Isotope-encoded spatial biology identifies plaque-age-dependent maturation and synaptic loss in an Alzheimer's disease mouse model","volume":"16","author":"Wood","year":"2025","journal-title":"Nat Commun"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-026-01538-4","article-title":"Hyperglycosylation is a metabolic driver of Alzheimer's disease","volume":"8","author":"Hawkinson","year":"2026","journal-title":"Nat Metab"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1419253","article-title":"Brain and serum lipidomic profiles implicate Lands cycle acyl chain remodeling association with APOE\u03f54 and mild cognitive impairment","volume":"16","author":"Mares","year":"2024","journal-title":"Front Aging Neurosci"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12675","article-title":"Predictive metabolic networks reveal sex- and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer's disease","volume":"19","author":"Chang","year":"2023","journal-title":"Alzheimers Dement"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.803894","article-title":"Application of CRISPR\/cas9 in alzheimer's disease","volume":"15","author":"Lu","year":"2021","journal-title":"Front Neurosci"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0037-25.2025","article-title":"Increasing H2B monoubiquitination improves the transcriptome and memory in the aged hippocampus","volume":"12","author":"Kincaid","year":"2025","journal-title":"eNeuro"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102394","article-title":"Delineation of the role of G6PD in Alzheimer's disease and potential enhancement through microfluidic and nanoparticle approaches","volume":"99","author":"Sharallah","year":"2024","journal-title":"Ageing Res Rev"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-026-01117-y","article-title":"Brain endothelial cell-derived extracellular vesicles (c-BEEVs) as a promising biomarker for brain vascular pathology and cognitive decline","volume":"6","author":"You","year":"2026","journal-title":"Nat Aging"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-022-01121-5","article-title":"Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: Results from the European Prevention of Alzheimer's Disease (EPAD) cohort","volume":"15","author":"Saleh","year":"2023","journal-title":"Alzheimers Res Ther"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.70139","article-title":"Sex differences and the role of estrogens in the immunological underpinnings of Alzheimer's disease","volume":"11","author":"Price","year":"2025","journal-title":"Alzheimers Dement (N Y)"},{"key":"B143","doi-asserted-by":"publisher","first-page":"105636","DOI":"10.1016\/j.neuint.2023.105636","article-title":"Estrogen receptor \u03b2 exerts neuroprotective effects by fine-tuning mitochondrial homeostasis through NRF1\/PGC-1\u03b1","author":"Zhao","year":"2023","journal-title":"Neurochem Int"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.3390\/cells12111549","article-title":"TREM2 agonism with a monoclonal antibody attenuates tau pathology and neurodegeneration","volume":"12","author":"Fassler","year":"2023","journal-title":"Cells"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-025-02092-3","article-title":"NLRP3 inflammasome and Alzheimer's disease: Bridging inflammation and neurodegeneration","volume":"34","author":"Wasim","year":"2026","journal-title":"Inflammopharmacology"},{"key":"B146","doi-asserted-by":"publisher","first-page":"795","DOI":"10.2174\/0118715273377780250505115039","article-title":"The NLRP3-P2X7 axis and cytokine crosstalk in Alzheimer's disease: Mechanisms, implications, and therapeutic opportunities","volume":"24","author":"Kurmi","year":"2025","journal-title":"CNS Neurol Disord Drug Targets"},{"key":"B147","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s12974-023-02791-0","article-title":"The involvement of NLRP3 inflammasome in CUMS-induced AD-like pathological changes and related cognitive decline in mice","volume":"20","author":"Li","year":"2023","journal-title":"J Neuroinflamm"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2024.117183","article-title":"The role of NLRP3 inflammasome-mediated neuroinflammation in chronic noise-induced impairment of learning and memory ability","volume":"286","author":"Ren","year":"2024","journal-title":"Ecotoxicol Environ Saf"},{"key":"B149","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s13205-021-02738-3","article-title":"Role of insulin receptor substance-1 modulating PI3K\/Akt insulin signaling pathway in Alzheimer's disease","volume":"11","author":"Zheng","year":"2021","journal-title":"3 Biotech"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2025.103107","article-title":"Emerging therapeutics targeting the PI3K\/Akt\/GSK-3\u03b2 in calcium dysregulation in Alzheimer's disease","volume":"133","author":"Soni","year":"2026","journal-title":"Cell Calcium"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.2025.2521721","article-title":"FGF21 restores metabolic function in Alzheimer's disease via activation of PI3K\/Akt signaling","volume":"48","author":"Zhao","year":"2026","journal-title":"Neurol Res"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.2174\/1871527322666230303114425","article-title":"APOE4 is a risk factor and potential therapeutic target for Alzheimer's disease","volume":"23","author":"Ayyubova","year":"2024","journal-title":"CNS Neurol Disord Drug Targets"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2023.11.023","article-title":"ApoE mimic peptide COG1410 reduces A\u03b2 deposition and improves cognitive function by inducing the transformation of A1\/A2 reactive astrocytes and increasing the BDNF concentration in brain of APP\/PS1 double transgenic mice","volume":"537","author":"Qiao","year":"2024","journal-title":"Neuroscience"},{"key":"B154","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-025-01031-9","article-title":"Exploratory analyses of clinical outcomes from the BIIB080 phase 1b study in mild Alzheimer's disease","volume":"6","author":"Shulman","year":"2026","journal-title":"Nat Aging"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.102162","article-title":"Lifestyle strategies to promote proteostasis and reduce the risk of Alzheimer's disease and other proteinopathies","volume":"93","author":"Almeida","year":"2024","journal-title":"Ageing Res Rev"},{"key":"B156","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-026-02122-0","article-title":"Spatial memory in Alzheimer's disease 5XFAD mice is enhanced by XPO1 inhibitor KPT-330","author":"Wong","year":"2026","journal-title":"Geroscience"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2025.1628835","article-title":"Beta-hydroxybutyrate (BHB) elicits concentration-dependent anti-inflammatory effects on microglial cells which are reversible by blocking its monocarboxylate (MCT) importer","volume":"6","author":"Garcia","year":"2025","journal-title":"Front Aging"},{"key":"B158","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.neurobiolaging.2019.09.015","article-title":"Modified ketogenic diet is associated with improved cerebrospinal fluid biomarker profile, cerebral perfusion, and cerebral ketone body uptake in older adults at risk for Alzheimer's disease: a pilot study","volume":"86","author":"Neth","year":"2020","journal-title":"Neurobiol Aging"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2024.148920","article-title":"Targeting VDAC: A potential therapeutic approach for mitochondrial dysfunction in Alzheimer's disease","volume":"1835","author":"Yang","year":"2024","journal-title":"Brain Res"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2026.110923","article-title":"Ajugol ameliorates mitochondrial dysfunction and cognitive decline in Alzheimer's disease via BNIP3-dependent mitophagy","volume":"291","author":"Qiao","year":"2026","journal-title":"Neuropharmacology"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2025.103692","article-title":"Cannabinol (CBN) alleviates age-related cognitive decline by improving synaptic and mitochondrial health","volume":"84","author":"Dar","year":"2025","journal-title":"Redox Biol"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR-D-25-00144","article-title":"Metabolic breakdown: Linking insulin resistance and mitochondrial dysfunction to neurodegeneration in Alzheimer's disease","volume":"21","author":"Lanzillotta","year":"2026","journal-title":"Neural Regener Res"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12866","article-title":"Associations among hypertension, dementia biomarkers, and cognition: The MEMENTO cohort","volume":"19","author":"Lespinasse","year":"2023","journal-title":"Alzheimers Dement"},{"key":"B164","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.1065117","article-title":"A combination of midlife diabetes mellitus and the apolipoprotein E \u03f54 allele increase risk for cognitive decline","volume":"14","author":"Lee","year":"2022","journal-title":"Front Aging Neurosci"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70739","article-title":"Relationship of antihypertensives with late-life cognitive decline and neuropathology","volume":"21","author":"Sood","year":"2025","journal-title":"Alzheimers Dement"},{"key":"B166","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1186\/s12967-022-03786-w","article-title":"Dyslipidemia induced large-scale network connectivity abnormality facilitates cognitive decline in the Alzheimer's disease","volume":"20","author":"Wang","year":"2022","journal-title":"J Transl Med"},{"key":"B167","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1184609","article-title":"Association between physical activity and episodic memory and the moderating effects of the apolipoprotein E \u03f54 allele and age","volume":"15","author":"Lee","year":"2023","journal-title":"Front Aging Neurosci"},{"key":"B168","doi-asserted-by":"publisher","first-page":"E164","DOI":"10.1152\/ajpendo.00008.2021","article-title":"Exercise and estrogen: common pathways in Alzheimer's disease pathology","volume":"321","author":"Bagit","year":"2021","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B169","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2023.578102","article-title":"Microglia activation mediates circadian rhythm disruption-induced cognitive impairment in mice","volume":"379","author":"Meng","year":"2023","journal-title":"J Neuroimmunol"},{"key":"B170","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1980-20.2020","article-title":"Zinc status alters Alzheimer's disease progression through NLRP3-dependent inflammation","volume":"41","author":"Rivers-Auty","year":"2021","journal-title":"J Neurosci"},{"key":"B171","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/s12974-025-03488-2","article-title":"Depression exacerbates AD pathology through lactate-dependent activation of microglial Kv1.3 to promote A\u03b2-containing exosome spreading","volume":"22","author":"Liu","year":"2025","journal-title":"J Neuroinflamm"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1925850\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:21:20Z","timestamp":1787217680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1925850\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":171,"alternative-id":["10.3389\/fimmu.2026.1925850"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1925850","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]},"article-number":"1925850"}}