{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T22:38:08Z","timestamp":1792881488215,"version":"4.5.0"},"reference-count":154,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":384,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100007457","name":"JPB Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007457","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002690","name":"Ruth K. Broad Biomedical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002690","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007625","name":"Cure Alzheimer's Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuron"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.neuron.2020.10.008","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T11:10:22Z","timestamp":1605006622000},"page":"205-221","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":283,"title":["Apolipoprotein E: Structural Insights and Links to Alzheimer Disease Pathogenesis"],"prefix":"10.1016","volume":"109","author":[{"given":"Yun","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Strickland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Soranno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Holtzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuron.2020.10.008_bib1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/0022-2836(88)90531-1","article-title":"Crystallization and preliminary X-ray diffraction studies on the amino-terminal (receptor-binding) domain of human apolipoprotein E3 from serum very low density lipoproteins","volume":"202","author":"Aggerbeck","year":"1988","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.neuron.2020.10.008_bib2","doi-asserted-by":"crossref","first-page":"10571","DOI":"10.1021\/bi9626362","article-title":"Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian cells with amyloid peptide beta (1-40). Relevance to Alzheimer\u2019s disease.\u03b2","volume":"36","author":"Aleshkov","year":"1997","journal-title":"Biochemistry"},{"key":"10.1016\/j.neuron.2020.10.008_bib3","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1038\/s41591-019-0611-3","article-title":"Resistance to autosomal dominant Alzheimer\u2019s disease in an APOE3 Christchurch homozygote: a case report","volume":"25","author":"Arboleda-Velasquez","year":"2019","journal-title":"Nat. Med."},{"key":"10.1016\/j.neuron.2020.10.008_bib4","doi-asserted-by":"crossref","first-page":"26043","DOI":"10.1074\/jbc.M115.679043","article-title":"Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)","volume":"290","author":"Atagi","year":"2015","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib5","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1016\/S0021-9258(19)41662-1","article-title":"The primary structure of human plasma high density apolipoprotein glutamine I (ApoA-I). II. The amino acid sequence and alignment of cyanogen bromide fragments IV, III, and I","volume":"250","author":"Baker","year":"1975","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib6","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/ng1197-263","article-title":"Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition","volume":"17","author":"Bales","year":"1997","journal-title":"Nat. Genet."},{"key":"10.1016\/j.neuron.2020.10.008_bib7","doi-asserted-by":"crossref","first-page":"15233","DOI":"10.1073\/pnas.96.26.15233","article-title":"Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer\u2019s disease","volume":"96","author":"Bales","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2020.10.008_bib8","doi-asserted-by":"crossref","first-page":"6771","DOI":"10.1523\/JNEUROSCI.0887-09.2009","article-title":"Human APOE isoform-dependent effects on brain beta-amyloid levels in PDAPP transgenic mice.\u03b2","volume":"29","author":"Bales","year":"2009","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.neuron.2020.10.008_bib9","doi-asserted-by":"crossref","first-page":"13959","DOI":"10.1074\/jbc.M111.288746","article-title":"Low-density lipoprotein receptor represents an apolipoprotein E-independent pathway of A\u03b2 uptake and degradation by astrocytes.\u03b2","volume":"287","author":"Basak","year":"2012","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib10","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/nature11087","article-title":"Apolipoprotein E controls cerebrovascular integrity via cyclophilin A","volume":"485","author":"Bell","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2020.10.008_bib11","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1042\/bj20020207","article-title":"Apolipoprotein E structural requirements for the formation of SDS-stable complexes with beta-amyloid-(1-40): the role of salt bridges","volume":"366","author":"Bentley","year":"2002","journal-title":"Biochem. J."},{"key":"10.1016\/j.neuron.2020.10.008_bib12","doi-asserted-by":"crossref","first-page":"4803","DOI":"10.1523\/JNEUROSCI.0033-12.2012","article-title":"Reducing human apolipoprotein E levels attenuates age-dependent A\u03b2 accumulation in mutant human amyloid precursor protein transgenic mice.\u03b2","volume":"32","author":"Bien-Ly","year":"2012","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.neuron.2020.10.008_bib13","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1016\/j.ajpath.2019.04.010","article-title":"Apolipoprotein E\/Amyloid-\u03b2 Complex Accumulates in Alzheimer Disease Cortical Synapses via Apolipoprotein E Receptors and Is Enhanced by APOE4.\u03b2","volume":"189","author":"Bilousova","year":"2019","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.neuron.2020.10.008_bib14","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1073\/pnas.80.1.283","article-title":"Apolipoprotein E synthesis in human kidney, adrenal gland, and liver","volume":"80","author":"Blue","year":"1983","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2020.10.008_bib15","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1172\/JCI112130","article-title":"Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system","volume":"76","author":"Boyles","year":"1985","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.neuron.2020.10.008_bib16","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/0006-291X(82)91927-1","article-title":"Apolipoprotein-E degradation in human very low density lipoproteins by plasma protease(s): chemical and biological consequences","volume":"109","author":"Bradley","year":"1982","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.neuron.2020.10.008_bib156","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1021\/bi00217a002","article-title":"Molecular Structure of an Apolipoprotein Determined at 2.5-\u00c5 Resolution","volume":"30","author":"Breiter","year":"1991","journal-title":"Biochemistry"},{"key":"10.1016\/j.neuron.2020.10.008_bib17","doi-asserted-by":"crossref","first-page":"563","DOI":"10.2353\/ajpath.2010.090973","article-title":"Cellular source of apolipoprotein E4 determines neuronal susceptibility to excitotoxic injury in transgenic mice","volume":"177","author":"Buttini","year":"2010","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.neuron.2020.10.008_bib18","doi-asserted-by":"crossref","first-page":"15464","DOI":"10.1074\/jbc.M500613200","article-title":"Rapid endocytosis of the low density lipoprotein receptor-related protein modulates cell surface distribution and processing of the beta-amyloid precursor protein.\u03b2","volume":"280","author":"Cam","year":"2005","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib19","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/0076-6879(91)03030-K","article-title":"Molecular design and modeling of protein-heparin interactions","volume":"203","author":"Cardin","year":"1991","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.neuron.2020.10.008_bib20","doi-asserted-by":"crossref","first-page":"17610","DOI":"10.1074\/jbc.270.29.17610","article-title":"Apolipoprotein E carboxyl-terminal fragments are complexed to amyloids A and L. Implications for amyloidogenesis and Alzheimer\u2019s disease","volume":"270","author":"Casta\u00f1o","year":"1995","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib21","doi-asserted-by":"crossref","first-page":"89ra57","DOI":"10.1126\/scitranslmed.3002156","article-title":"Human apoE isoforms differentially regulate brain amyloid-\u03b2 peptide clearance.\u03b2","volume":"3","author":"Castellano","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.neuron.2020.10.008_bib22","doi-asserted-by":"crossref","first-page":"15502","DOI":"10.1073\/pnas.1206446109","article-title":"Low-density lipoprotein receptor overexpression enhances the rate of brain-to-blood A\u03b2 clearance in a mouse model of \u03b2-amyloidosis.\u03b2\u03b2","volume":"109","author":"Castellano","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2020.10.008_bib23","doi-asserted-by":"crossref","first-page":"14813","DOI":"10.1073\/pnas.1106420108","article-title":"Topology of human apolipoprotein E3 uniquely regulates its diverse biological functions","volume":"108","author":"Chen","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2020.10.008_bib24","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1126\/science.8346443","article-title":"Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer\u2019s disease in late onset families","volume":"261","author":"Corder","year":"1993","journal-title":"Science"},{"key":"10.1016\/j.neuron.2020.10.008_bib25","first-page":"100","article-title":"Apolipoprotein E polymorphism and atherosclerosis: insight from a study in octogenarians","volume":"99","author":"Davignon","year":"1988","journal-title":"Trans. Am. Clin. Climatol. Assoc."},{"key":"10.1016\/j.neuron.2020.10.008_bib26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1126\/scitranslmed.aay3069","article-title":"APOE genotype regulates pathology and disease progression in synucleinopathy","volume":"12","author":"Davis","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.neuron.2020.10.008_bib27","doi-asserted-by":"crossref","first-page":"4206","DOI":"10.1074\/jbc.273.7.4206","article-title":"A minimally lipidated form of cell-derived apolipoprotein E exhibits isoform-specific stimulation of neurite outgrowth in the absence of exogenous lipids or lipoproteins","volume":"273","author":"DeMattos","year":"1998","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib28","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/S0022-2275(20)31622-9","article-title":"Biochemical analysis of cell-derived apoE3 particles active in stimulating neurite outgrowth","volume":"42","author":"DeMattos","year":"2001","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.neuron.2020.10.008_bib29","doi-asserted-by":"crossref","first-page":"e1182","DOI":"10.1212\/WNL.0000000000006212","article-title":"APOE \u03b54 is associated with severity of Lewy body pathology independent of Alzheimer pathology.\u03b5","volume":"91","author":"Dickson","year":"2018","journal-title":"Neurology"},{"key":"10.1016\/j.neuron.2020.10.008_bib30","doi-asserted-by":"crossref","first-page":"19053","DOI":"10.1074\/jbc.271.32.19053","article-title":"Human apolipoprotein E4 domain interaction. Arginine 61 and glutamic acid 255 interact to direct the preference for very low density lipoproteins","volume":"271","author":"Dong","year":"1996","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib31","doi-asserted-by":"crossref","first-page":"22358","DOI":"10.1016\/S0021-9258(17)31797-0","article-title":"Human apolipoprotein E. Role of arginine 61 in mediating the lipoprotein preferences of the E3 and E4 isoforms","volume":"269","author":"Dong","year":"1994","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib32","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1021\/bi002417n","article-title":"Interaction of the N-terminal domain of apolipoprotein E4 with heparin","volume":"40","author":"Dong","year":"2001","journal-title":"Biochemistry"},{"key":"10.1016\/j.neuron.2020.10.008_bib33","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.2337\/diab.36.11.1301","article-title":"Increased frequency of apolipoprotein epsilon 4 allele in type II diabetes with hypercholesterolemia","volume":"36","author":"Eto","year":"1987","journal-title":"Diabetes"},{"key":"10.1016\/j.neuron.2020.10.008_bib34","doi-asserted-by":"crossref","first-page":"127","DOI":"10.2337\/diacare.14.2.127","article-title":"Relationship of metabolic control and body weight to hypercholesterolemia in NIDDM patients with apolipoprotein E4","volume":"14","author":"Eto","year":"1991","journal-title":"Diabetes Care"},{"key":"10.1016\/j.neuron.2020.10.008_bib35","doi-asserted-by":"crossref","first-page":"30001","DOI":"10.1074\/jbc.274.42.30001","article-title":"Unique lipoproteins secreted by primary astrocytes from wild type, apoE (-\/-), and human apoE transgenic mice","volume":"274","author":"Fagan","year":"1999","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib36","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1006\/nbdi.2002.0483","article-title":"Human and murine ApoE markedly alters A beta metabolism before and after plaque formation in a mouse model of Alzheimer\u2019s disease","volume":"9","author":"Fagan","year":"2002","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.neuron.2020.10.008_bib37","doi-asserted-by":"crossref","first-page":"33601","DOI":"10.1074\/jbc.M002643200","article-title":"The lipid-associated conformation of the low density lipoprotein receptor binding domain of human apolipoprotein E","volume":"275","author":"Fisher","year":"2000","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib38","doi-asserted-by":"crossref","first-page":"6862","DOI":"10.1523\/JNEUROSCI.1051-10.2010","article-title":"Liver X receptor agonist treatment ameliorates amyloid pathology and memory deficits caused by high-fat diet in APP23 mice","volume":"30","author":"Fitz","year":"2010","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.neuron.2020.10.008_bib39","doi-asserted-by":"crossref","first-page":"6292","DOI":"10.1073\/pnas.1705080114","article-title":"A mechanism for lipid binding to apoE and the role of intrinsically disordered regions coupled to domain-domain interactions","volume":"114","author":"Frieden","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2020.10.008_bib40","doi-asserted-by":"crossref","first-page":"25754","DOI":"10.1074\/jbc.M502143200","article-title":"The low density lipoprotein receptor regulates the level of central nervous system human and murine apolipoprotein E but does not modify amyloid plaque pathology in PDAPP mice","volume":"280","author":"Fryer","year":"2005","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib41","doi-asserted-by":"crossref","first-page":"5414","DOI":"10.1074\/jbc.M411719200","article-title":"Two-step mechanism of binding of apolipoprotein E to heparin: implications for the kinetics of apolipoprotein E-heparan sulfate proteoglycan complex formation on cell surfaces","volume":"280","author":"Futamura","year":"2005","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib42","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1021\/bi1020106","article-title":"Dissociation of apolipoprotein E oligomers to monomer is required for high-affinity binding to phospholipid vesicles","volume":"50","author":"Garai","year":"2011","journal-title":"Biochemistry"},{"key":"10.1016\/j.neuron.2020.10.008_bib43","doi-asserted-by":"crossref","first-page":"6323","DOI":"10.1021\/bi5008172","article-title":"The binding of apolipoprotein E to oligomers and fibrils of amyloid-\u03b2 alters the kinetics of amyloid aggregation","volume":"53","author":"Garai","year":"2014","journal-title":"Biochemistry"},{"key":"10.1016\/j.neuron.2020.10.008_bib44","doi-asserted-by":"crossref","first-page":"4737","DOI":"10.1111\/febs.14988","article-title":"High-affinity multivalent interactions between apolipoprotein E and the oligomers of amyloid-\u03b2","volume":"286","author":"Ghosh","year":"2019","journal-title":"FEBS J."},{"key":"10.1016\/j.neuron.2020.10.008_bib45","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/B978-0-12-152811-9.50011-0","article-title":"The LDL pathway in human fibroblasts: a receptor-mediated mechanism for the regulation of cholesterol metabolism","volume":"11","author":"Goldstein","year":"1976","journal-title":"Curr. Top. Cell. Regul."},{"key":"10.1016\/j.neuron.2020.10.008_bib46","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1194\/jlr.R076331","article-title":"Omega-3 fatty acids, lipids, and apoE lipidation in Alzheimer\u2019s disease: a rationale for multi-nutrient dementia prevention","volume":"58","author":"Grimm","year":"2017","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.neuron.2020.10.008_bib47","doi-asserted-by":"crossref","first-page":"35831","DOI":"10.1074\/jbc.M706425200","article-title":"Structural basis for the recognition and cross-linking of amyloid fibrils by human apolipoprotein E","volume":"282","author":"Gunzburg","year":"2007","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib48","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.jmb.2010.03.022","article-title":"Structure of the minimal interface between ApoE and LRP","volume":"398","author":"Guttman","year":"2010","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.neuron.2020.10.008_bib49","doi-asserted-by":"crossref","first-page":"15181","DOI":"10.1523\/JNEUROSCI.1542-12.2012","article-title":"Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid \u03b2 peptide.\u03b2","volume":"32","author":"Hashimoto","year":"2012","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.neuron.2020.10.008_bib50","doi-asserted-by":"crossref","first-page":"26477","DOI":"10.1074\/jbc.M503910200","article-title":"Engineering conformational destabilization into mouse apolipoprotein E. A model for a unique property of human apolipoprotein E4","volume":"280","author":"Hatters","year":"2005","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib51","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.tibs.2006.06.008","article-title":"Apolipoprotein E structure: insights into function","volume":"31","author":"Hatters","year":"2006","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.neuron.2020.10.008_bib52","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jmb.2008.12.040","article-title":"Insight on the molecular envelope of lipid-bound apolipoprotein E from electron paramagnetic resonance spectroscopy","volume":"386","author":"Hatters","year":"2009","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.neuron.2020.10.008_bib53","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1093\/jnen\/nlw067","article-title":"Apolipoprotein E Genotype Affects Size of ApoE Complexes in Cerebrospinal Fluid","volume":"75","author":"Heinsinger","year":"2016","journal-title":"J.\u00a0Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.neuron.2020.10.008_bib54","doi-asserted-by":"crossref","first-page":"e1006165","DOI":"10.1371\/journal.pcbi.1006165","article-title":"Lipidated apolipoprotein E4 structure and its receptor binding mechanism determined by a combined cross-linking coupled to mass spectrometry and molecular dynamics approach","volume":"14","author":"Henry","year":"2018","journal-title":"PLoS Comput. Biol."},{"key":"10.1016\/j.neuron.2020.10.008_bib55","doi-asserted-by":"crossref","first-page":"41197","DOI":"10.1074\/jbc.M407962200","article-title":"Deficiency of ABCA1 impairs apolipoprotein E metabolism in brain","volume":"279","author":"Hirsch-Reinshagen","year":"2004","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib56","doi-asserted-by":"crossref","first-page":"43243","DOI":"10.1074\/jbc.M508781200","article-title":"The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease","volume":"280","author":"Hirsch-Reinshagen","year":"2005","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib57","doi-asserted-by":"crossref","first-page":"R15","DOI":"10.1172\/JCI6179","article-title":"Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer\u2019s disease","volume":"103","author":"Holtzman","year":"1999","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.neuron.2020.10.008_bib58","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1073\/pnas.050004797","article-title":"Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer\u2019s disease","volume":"97","author":"Holtzman","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2020.10.008_bib59","doi-asserted-by":"crossref","first-page":"a006312","DOI":"10.1101\/cshperspect.a006312","article-title":"Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease","volume":"2","author":"Holtzman","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"10.1016\/j.neuron.2020.10.008_bib60","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13024-015-0001-3","article-title":"Opposing effects of viral mediated brain expression of apolipoprotein E2 (apoE2) and apoE4 on apoE lipidation and A\u03b2 metabolism in apoE4-targeted replacement mice.\u03b2","volume":"10","author":"Hu","year":"2015","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.neuron.2020.10.008_bib61","doi-asserted-by":"crossref","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.\u03b2","volume":"168","author":"Huang","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.neuron.2020.10.008_bib62","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.arr.2017.06.002","article-title":"Evolution of human apolipoprotein E (APOE) isoforms: Gene structure, protein function and interaction with dietary factors","volume":"37","author":"Huebbe","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.neuron.2020.10.008_bib63","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/S0021-9258(17)43536-8","article-title":"Defective hepatic lipoprotein receptor binding of beta-very low density lipoproteins from type III hyperlipoproteinemic patients. Importance of apolipoprotein E.\u03b2","volume":"259","author":"Hui","year":"1984","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib64","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.neuron.2017.11.014","article-title":"Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of \u03b2-amyloidosis","volume":"96","author":"Huynh","year":"2017","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2020.10.008_bib65","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13024-019-0337-1","article-title":"Lack of hepatic apoE does not influence early A\u03b2 deposition: observations from a new APOE knock-in model.\u03b2","volume":"14","author":"Huynh","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.neuron.2020.10.008_bib66","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1021\/bi00601a013","article-title":"Enhanced binding by cultured human fibroblasts of apo-E-containing lipoproteins as compared with low density lipoproteins","volume":"17","author":"Innerarity","year":"1978","journal-title":"Biochemistry"},{"key":"10.1016\/j.neuron.2020.10.008_bib67","doi-asserted-by":"crossref","first-page":"4186","DOI":"10.1016\/S0021-9258(18)50713-4","article-title":"Binding of arginine-rich (E) apoprotein after recombination with phospholipid vesicles to the low density lipoprotein receptors of fibroblasts","volume":"254","author":"Innerarity","year":"1979","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib68","doi-asserted-by":"crossref","first-page":"12341","DOI":"10.1016\/S0021-9258(17)44180-9","article-title":"The receptor-binding domain of human apolipoprotein E. Binding of apolipoprotein E fragments","volume":"258","author":"Innerarity","year":"1983","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib69","doi-asserted-by":"crossref","first-page":"7261","DOI":"10.1016\/S0021-9258(17)39866-6","article-title":"Normalization of receptor binding of apolipoprotein E2. Evidence for modulation of the binding site conformation","volume":"259","author":"Innerarity","year":"1984","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib70","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/BF01731865","article-title":"The mechanism of lipid-binding by plasma lipoproteins","volume":"6","author":"Jackson","year":"1975","journal-title":"Mol. Cell. Biochem."},{"key":"10.1016\/j.neuron.2020.10.008_bib71","doi-asserted-by":"crossref","first-page":"21821","DOI":"10.1074\/jbc.M112109200","article-title":"Apolipoprotein E4 potentiates amyloid beta peptide-induced lysosomal leakage and apoptosis in neuronal cells","volume":"277","author":"Ji","year":"2002","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib72","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1074\/jbc.M506646200","article-title":"Reactivity of apolipoprotein E4 and amyloid beta peptide: lysosomal stability and neurodegeneration","volume":"281","author":"Ji","year":"2006","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib73","doi-asserted-by":"crossref","first-page":"e14586","DOI":"10.1371\/journal.pone.0014586","article-title":"Apolipoprotein E: isoform specific differences in tertiary structure and interaction with amyloid-\u03b2 in human Alzheimer brain","volume":"6","author":"Jones","year":"2011","journal-title":"PLoS ONE"},{"key":"10.1016\/j.neuron.2020.10.008_bib74","doi-asserted-by":"crossref","first-page":"19276","DOI":"10.1523\/JNEUROSCI.3487-13.2013","article-title":"Neuronal clearance of amyloid-\u03b2 by endocytic receptor LRP1","volume":"33","author":"Kanekiyo","year":"2013","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.neuron.2020.10.008_bib75","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.neuron.2009.11.013","article-title":"Overexpression of low-density lipoprotein receptor in the brain markedly inhibits amyloid deposition and increases extracellular A beta clearance","volume":"64","author":"Kim","year":"2009","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2020.10.008_bib76","doi-asserted-by":"crossref","first-page":"18007","DOI":"10.1523\/JNEUROSCI.3773-11.2011","article-title":"Haploinsufficiency of human APOE reduces amyloid deposition in a mouse model of amyloid-\u03b2 amyloidosis.\u03b2","volume":"31","author":"Kim","year":"2011","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.neuron.2020.10.008_bib77","doi-asserted-by":"crossref","first-page":"43224","DOI":"10.1074\/jbc.M504513200","article-title":"Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 mice","volume":"280","author":"Koldamova","year":"2005","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib78","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.immuni.2017.08.008","article-title":"The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases","volume":"47","author":"Krasemann","year":"2017","journal-title":"Immunity"},{"key":"10.1016\/j.neuron.2020.10.008_bib79","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1194\/jlr.M300418-JLR200","article-title":"Molecular interactions between apoE and ABCA1: impact on apoE lipidation","volume":"45","author":"Krimbou","year":"2004","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.neuron.2020.10.008_bib80","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1016\/j.ajpath.2013.01.034","article-title":"Blocking the interaction between apolipoprotein E and A\u03b2 reduces intraneuronal accumulation of A\u03b2 and inhibits synaptic degeneration","volume":"182","author":"Kuszczyk","year":"2013","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.neuron.2020.10.008_bib81","doi-asserted-by":"crossref","first-page":"23403","DOI":"10.1016\/S0021-9258(17)31529-6","article-title":"Isoform-specific binding of apolipoprotein E to \u03b2-amyloid","volume":"269","author":"LaDu","year":"1994","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib82","doi-asserted-by":"crossref","first-page":"9039","DOI":"10.1074\/jbc.270.16.9039","article-title":"Purification of apolipoprotein E attenuates isoform-specific binding to beta-amyloid","volume":"270","author":"LaDu","year":"1995","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib83","doi-asserted-by":"crossref","first-page":"3542","DOI":"10.1016\/S0021-9258(18)68957-4","article-title":"Site-specific mutagenesis of human apolipoprotein E. Receptor binding activity of variants with single amino acid substitutions","volume":"263","author":"Lalazar","year":"1988","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib84","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1172\/JCI118883","article-title":"Regulation of scavenger receptor, class B, type I, a high density lipoprotein receptor, in liver and steroidogenic tissues of the rat","volume":"98","author":"Landschulz","year":"1996","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.neuron.2020.10.008_bib85","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0022-2275(20)38532-1","article-title":"The apolipoprotein multigene family: biosynthesis, structure, structure-function relationships, and evolution","volume":"29","author":"Li","year":"1988","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.neuron.2020.10.008_bib86","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1172\/JCI96429","article-title":"Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation","volume":"128","author":"Liao","year":"2018","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.neuron.2020.10.008_bib87","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy","volume":"9","author":"Liu","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.neuron.2020.10.008_bib88","doi-asserted-by":"crossref","first-page":"4023","DOI":"10.1523\/JNEUROSCI.3442-16.2017","article-title":"Astrocytic LRP1 Mediates Brain A\u03b2 Clearance and Impacts Amyloid Deposition.\u03b2","volume":"37","author":"Liu","year":"2017","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.neuron.2020.10.008_bib89","doi-asserted-by":"crossref","first-page":"11628","DOI":"10.1074\/jbc.M112.411900","article-title":"Binding of apolipoprotein E inhibits the oligomer growth of amyloid-\u03b2 peptide in solution as determined by fluorescence cross-correlation spectroscopy.\u03b2","volume":"288","author":"Ly","year":"2013","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib90","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/372092a0","article-title":"Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments","volume":"372","author":"Ma","year":"1994","journal-title":"Nature"},{"key":"10.1016\/j.neuron.2020.10.008_bib91","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1126\/science.3283935","article-title":"Apolipoprotein E: cholesterol transport protein with expanding role in cell biology","volume":"240","author":"Mahley","year":"1988","journal-title":"Science"},{"key":"10.1016\/j.neuron.2020.10.008_bib92","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.neuron.2012.11.020","article-title":"Apolipoprotein e sets the stage: response to injury triggers neuropathology","volume":"76","author":"Mahley","year":"2012","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2020.10.008_bib93","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0005-2760(79)90133-4","article-title":"Interaction of plasma lipoproteins containing apolipoproteins B and E with heparin and cell surface receptors","volume":"575","author":"Mahley","year":"1979","journal-title":"Biochim. Biophys. Acta"},{"issue":"Suppl","key":"10.1016\/j.neuron.2020.10.008_bib94","doi-asserted-by":"crossref","first-page":"S183","DOI":"10.1194\/jlr.R800069-JLR200","article-title":"Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer\u2019s disease to AIDS","volume":"50","author":"Mahley","year":"2009","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.neuron.2020.10.008_bib95","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/0005-2760(89)90043-X","article-title":"Apolipoprotein E-1Harrisburg: a new variant of apolipoprotein E dominantly associated with type III hyperlipoproteinemia","volume":"1005","author":"Mann","year":"1989","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.neuron.2020.10.008_bib97","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/ana.21843","article-title":"APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging","volume":"67","author":"Morris","year":"2010","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neuron.2020.10.008_bib98","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1074\/jbc.275.4.2576","article-title":"Effect of arginine 172 on the binding of apolipoprotein E to the low density lipoprotein receptor","volume":"275","author":"Morrow","year":"2000","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib99","doi-asserted-by":"crossref","first-page":"50380","DOI":"10.1074\/jbc.M204898200","article-title":"Apolipoprotein E4 forms a molten globule. A potential basis for its association with disease","volume":"277","author":"Morrow","year":"2002","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib100","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0896-6273(95)90079-9","article-title":"Characterization of stable complexes involving apolipoprotein E and the amyloid beta peptide in Alzheimer\u2019s disease brain","volume":"15","author":"N\u00e4slund","year":"1995","journal-title":"Neuron"},{"key":"10.1016\/j.neuron.2020.10.008_bib101","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1016\/S0021-9258(18)89575-8","article-title":"Quantitation of apolipoprotein E mRNA in the liver and peripheral tissues of nonhuman primates","volume":"260","author":"Newman","year":"1985","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib102","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/s41593-018-0296-9","article-title":"Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE","volume":"22","author":"Parhizkar","year":"2019","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neuron.2020.10.008_bib103","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1074\/jbc.M510851200","article-title":"Model of biologically active apolipoprotein E bound to dipalmitoylphosphatidylcholine","volume":"281","author":"Peters-Libeu","year":"2006","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib104","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/0005-2760(87)90295-5","article-title":"Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins","volume":"917","author":"Pitas","year":"1987","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.neuron.2020.10.008_bib105","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1172\/JCI110829","article-title":"Identical structural and receptor binding defects in apolipoprotein E2 in hypo-, normo-, and hypercholesterolemic dysbetalipoproteinemia","volume":"71","author":"Rall","year":"1983","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.neuron.2020.10.008_bib106","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1016\/j.jmb.2019.04.019","article-title":"The Molecular Basis for Apolipoprotein E4 as the Major Risk Factor for Late-Onset Alzheimer\u2019s Disease","volume":"431","author":"Raulin","year":"2019","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.neuron.2020.10.008_bib107","doi-asserted-by":"crossref","first-page":"25825","DOI":"10.1074\/jbc.273.40.25825","article-title":"The low density lipoprotein receptor active conformation of apolipoprotein E. Helix organization in n-terminal domain-phospholipid disc particles","volume":"273","author":"Raussens","year":"1998","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib108","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1016\/j.bpj.2017.10.006","article-title":"Atomistic Insights into Structural Differences between E3 and E4 Isoforms of Apolipoprotein E","volume":"113","author":"Ray","year":"2017","journal-title":"Biophys. J."},{"key":"10.1016\/j.neuron.2020.10.008_bib109","doi-asserted-by":"crossref","first-page":"6820","DOI":"10.1073\/pnas.0900345106","article-title":"Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer\u2019s disease","volume":"106","author":"Reiman","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2020.10.008_bib110","doi-asserted-by":"crossref","first-page":"23227","DOI":"10.1074\/jbc.M303365200","article-title":"Domain structure and lipid interaction in human apolipoproteins A-I and E, a general model","volume":"278","author":"Saito","year":"2003","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib111","first-page":"41","article-title":"\u201cEffect of apo\u00fcpoprotein E4 al\u00edele on plasma LDLcholesterol response to diet therapy in type 2 diabetic patients\u201d. Apunts","volume":"39","author":"Saito","year":"2004","journal-title":"Medicina de L\u2019Esport"},{"key":"10.1016\/j.neuron.2020.10.008_bib112","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1172\/JCI117407","article-title":"Apolipoprotein E associates with \u03b2 amyloid peptide of Alzheimer\u2019s disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3","volume":"94","author":"Sanan","year":"1994","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.neuron.2020.10.008_bib113","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0022-2275(20)41536-6","article-title":"The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function","volume":"33","author":"Segrest","year":"1992","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.neuron.2020.10.008_bib114","doi-asserted-by":"crossref","first-page":"14531","DOI":"10.1021\/bi970558s","article-title":"Infrared spectroscopy of human apolipoprotein fragments in SDS\/D2O: relative lipid-binding affinities and a novel amide I assignment","volume":"36","author":"Shaw","year":"1997","journal-title":"Biochemistry"},{"key":"10.1016\/j.neuron.2020.10.008_bib115","doi-asserted-by":"crossref","first-page":"523","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":"10.1016\/j.neuron.2020.10.008_bib116","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1084\/jem.20190980","article-title":"Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model","volume":"216","author":"Shi","year":"2019","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.neuron.2020.10.008_bib117","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1021\/bi00727a022","article-title":"Heterogeneity of human plasma very low density lipoproteins. Separation of species differing in protein components","volume":"12","author":"Shore","year":"1973","journal-title":"Biochemistry"},{"key":"10.1016\/j.neuron.2020.10.008_bib119","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1021\/bi00119a015","article-title":"Apolipoprotein E: phospholipid binding studies with synthetic peptides from the carboxyl terminus","volume":"31","author":"Sparrow","year":"1992","journal-title":"Biochemistry"},{"key":"10.1016\/j.neuron.2020.10.008_bib120","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1073\/pnas.90.5.1977","article-title":"Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease","volume":"90","author":"Strittmatter","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2020.10.008_bib121","doi-asserted-by":"crossref","first-page":"8098","DOI":"10.1073\/pnas.90.17.8098","article-title":"Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease","volume":"90","author":"Strittmatter","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2020.10.008_bib122","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1172\/JCI124853","article-title":"APOE4-mediated amyloid-\u03b2 pathology depends on its neuronal receptor LRP1","volume":"129","author":"Tachibana","year":"2019","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.neuron.2020.10.008_bib123","doi-asserted-by":"crossref","first-page":"5914","DOI":"10.1074\/jbc.M112.442103","article-title":"Levels of soluble apolipoprotein E\/amyloid-\u03b2 (A\u03b2) complex are reduced and oligomeric A\u03b2 increased with APOE4 and Alzheimer disease in a transgenic mouse model and human samples","volume":"288","author":"Tai","year":"2013","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib124","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1001\/jamaneurol.2013.600","article-title":"APOE \u03b54 increases risk for dementia in pure synucleinopathies.\u03b5","volume":"70","author":"Tsuang","year":"2013","journal-title":"JAMA Neurol."},{"key":"10.1016\/j.neuron.2020.10.008_bib125","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1084\/jem.20171265","article-title":"ApoE facilitates the microglial response to amyloid plaque pathology","volume":"215","author":"Ulrich","year":"2018","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.neuron.2020.10.008_bib126","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1515\/bchm2.1975.356.2.1113","article-title":"Isolation and partial characterization of an arginine-rich apolipoprotein from human plasma very-low-density lipoproteins: apolipoprotein E","volume":"356","author":"Utermann","year":"1975","journal-title":"Hoppe Seylers Z. Physiol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib127","doi-asserted-by":"crossref","first-page":"E1807","DOI":"10.1073\/pnas.1220484110","article-title":"ApoE influences amyloid-\u03b2 (A\u03b2) clearance despite minimal apoE\/A\u03b2 association in physiological conditions","volume":"110","author":"Verghese","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.neuron.2020.10.008_bib128","doi-asserted-by":"crossref","first-page":"40987","DOI":"10.1074\/jbc.M407963200","article-title":"ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE","volume":"279","author":"Wahrle","year":"2004","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib129","doi-asserted-by":"crossref","first-page":"43236","DOI":"10.1074\/jbc.M508780200","article-title":"Deletion of Abca1 increases Abeta deposition in the PDAPP transgenic mouse model of Alzheimer disease","volume":"280","author":"Wahrle","year":"2005","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib130","first-page":"671","article-title":"Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease","volume":"118","author":"Wahrle","year":"2008","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.neuron.2020.10.008_bib131","doi-asserted-by":"crossref","first-page":"10358","DOI":"10.1021\/bi960934t","article-title":"Conformations of human apolipoprotein E(263-286) and E(267-289) in aqueous solutions of sodium dodecyl sulfate by CD and 1H NMR","volume":"35","author":"Wang","year":"1996","journal-title":"Biochemistry"},{"key":"10.1016\/j.neuron.2020.10.008_bib133","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/s41591-018-0004-z","article-title":"Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector","volume":"24","author":"Wang","year":"2018","journal-title":"Nat. Med."},{"key":"10.1016\/j.neuron.2020.10.008_bib132","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/0005-2760(96)00037-9","article-title":"Conformation of human serum apolipoprotein A-I(166-185) in the presence of sodium dodecyl sulfate or dodecylphosphocholine by 1H-NMR and CD. Evidence for specific peptide-SDS interactions","volume":"1301","author":"Wang","year":"1996","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.neuron.2020.10.008_bib134","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/S0022-2275(20)38055-X","article-title":"Genetic variation in human apolipoprotein E","volume":"23","author":"Wardell","year":"1982","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.neuron.2020.10.008_bib135","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/S0022-2275(20)42621-5","article-title":"Apolipoprotein E distribution among human plasma lipoproteins: role of the cysteine-arginine interchange at residue 112","volume":"31","author":"Weisgraber","year":"1990","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.neuron.2020.10.008_bib136","series-title":"Advances in Protein Chemistry","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0065-3233(08)60642-7","article-title":"Apolipoprotein E: Structure-Function Relationships","author":"Weisgraber","year":"1994"},{"key":"10.1016\/j.neuron.2020.10.008_bib137","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1016\/S0021-9258(18)34954-8","article-title":"Abnormal lipoprotein receptor-binding activity of the human E apoprotein due to cysteine-arginine interchange at a single site","volume":"257","author":"Weisgraber","year":"1982","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib138","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1016\/S0021-9258(18)32955-7","article-title":"Apolipoprotein A-IMilano. Detection of normal A-I in affected subjects and evidence for a cysteine for arginine substitution in the variant A-I","volume":"258","author":"Weisgraber","year":"1983","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib139","doi-asserted-by":"crossref","first-page":"9094","DOI":"10.1016\/S0021-9258(18)81907-X","article-title":"Glycosylation of human apolipoprotein E. The carbohydrate attachment site is threonine 194","volume":"264","author":"Wernette-Hammond","year":"1989","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib140","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1016\/S0021-9258(18)89574-6","article-title":"Apolipoprotein E synthesis in peripheral tissues of nonhuman primates","volume":"260","author":"Williams","year":"1985","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib141","doi-asserted-by":"crossref","first-page":"e1004359","DOI":"10.1371\/journal.pcbi.1004359","article-title":"ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations","volume":"11","author":"Williams","year":"2015","journal-title":"PLoS Comput. Biol."},{"key":"10.1016\/j.neuron.2020.10.008_bib142","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1126\/science.2063194","article-title":"Three-dimensional structure of the LDL receptor-binding domain of human apolipoprotein E","volume":"252","author":"Wilson","year":"1991","journal-title":"Science"},{"key":"10.1016\/j.neuron.2020.10.008_bib143","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0969-2126(00)00072-1","article-title":"Salt bridge relay triggers defective LDL receptor binding by a mutant apolipoprotein","volume":"2","author":"Wilson","year":"1994","journal-title":"Structure"},{"key":"10.1016\/j.neuron.2020.10.008_bib144","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0022-2275(20)32449-4","article-title":"Competition of Abeta amyloid peptide and apolipoprotein E for receptor-mediated endocytosis","volume":"40","author":"Winkler","year":"1999","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.neuron.2020.10.008_bib145","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0304-3940(92)90444-C","article-title":"Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid","volume":"135","author":"Wisniewski","year":"1992","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.neuron.2020.10.008_bib146","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1006\/bbrc.1993.1423","article-title":"Apolipoprotein E: binding to soluble Alzheimer\u2019s beta-amyloid","volume":"192","author":"Wisniewski","year":"1993","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.neuron.2020.10.008_bib147","doi-asserted-by":"crossref","first-page":"25511","DOI":"10.1074\/jbc.M311256200","article-title":"Apolipoprotein E4 domain interaction occurs in living neuronal cells as determined by fluorescence resonance energy transfer","volume":"279","author":"Xu","year":"2004","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib148","doi-asserted-by":"crossref","first-page":"680","DOI":"10.2353\/ajpath.2007.060378","article-title":"Interferon-gamma and tumor necrosis factor-alpha regulate amyloid-beta plaque deposition and beta-secretase expression in Swedish mutant APP transgenic mice","volume":"170","author":"Yamamoto","year":"2007","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.neuron.2020.10.008_bib149","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.ab.2007.09.005","article-title":"Apolipoprotein E isoform-specific binding to the low-density lipoprotein receptor","volume":"372","author":"Yamamoto","year":"2008","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.neuron.2020.10.008_bib150","doi-asserted-by":"crossref","first-page":"6702","DOI":"10.1021\/bi8003999","article-title":"Role of the N- and C-terminal domains in binding of apolipoprotein E isoforms to heparan sulfate and dermatan sulfate: a surface plasmon resonance study","volume":"47","author":"Yamauchi","year":"2008","journal-title":"Biochemistry"},{"key":"10.1016\/j.neuron.2020.10.008_bib151","doi-asserted-by":"crossref","first-page":"41774","DOI":"10.1074\/jbc.M112.407957","article-title":"APOE4-specific changes in A\u03b2 accumulation in a new transgenic mouse model of Alzheimer disease","volume":"287","author":"Youmans","year":"2012","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.neuron.2020.10.008_bib152","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1194\/jlr.D002493","article-title":"An optimized negative-staining protocol of electron microscopy for apoE4 POPC lipoprotein","volume":"51","author":"Zhang","year":"2010","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.neuron.2020.10.008_bib153","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1016\/j.bbagen.2012.09.016","article-title":"Optimized negative-staining electron microscopy for lipoprotein studies","volume":"1830","author":"Zhang","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.neuron.2020.10.008_bib154","doi-asserted-by":"crossref","first-page":"4388","DOI":"10.1038\/s41467-018-06783-0","article-title":"APOE \u03b52 is associated with increased tau pathology in primary tauopathy","volume":"9","author":"Zhao","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.neuron.2020.10.008_bib155","doi-asserted-by":"crossref","first-page":"eaay1809","DOI":"10.1126\/scitranslmed.aay1809","article-title":"APOE4 exacerbates -synuclein pathology and related toxicity independent of amyloid","volume":"12","author":"Zhao","year":"2020","journal-title":"Sci. Trans. Med."}],"container-title":["Neuron"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0896627320307765?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0896627320307765?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T07:30:29Z","timestamp":1760254229000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0896627320307765"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":154,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["S0896627320307765"],"URL":"https:\/\/doi.org\/10.1016\/j.neuron.2020.10.008","relation":{},"ISSN":["0896-6273"],"issn-type":[{"value":"0896-6273","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Apolipoprotein E: Structural Insights and Links to Alzheimer Disease Pathogenesis","name":"articletitle","label":"Article Title"},{"value":"Neuron","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neuron.2020.10.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Inc.","name":"copyright","label":"Copyright"}]}}