Attems J, Jellinger KA, Lintner F. Alzheimer’s disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy. Acta Neuropathol. 2005;110:222–31.

Article  PubMed  Google Scholar 

Long JM, Holtzman DM. Alzheimer disease: an update on pathobiology and treatment strategies. Cell. 2019;179:312–39.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hanseeuw BJ, Betensky RA, Jacobs HIL, Schultz AP, Sepulcre J, Becker JA, Cosio DMO, Farrell M, Quiroz YT, Mormino EC, Buckley RF, Papp KV, Amariglio RA, Dewachter I, Ivanoiu A, Huijbers W, Hedden T, Marshall GA, Chhatwal JP, Rentz DM, Sperling RA, Johnson K. Association of Amyloid and Tau with cognition in preclinical alzheimer disease: a longitudinal study. JAMA Neurol. 2019;76:915–24.

Article  PubMed  PubMed Central  Google Scholar 

Greenberg SM, Bacskai BJ, Hernandez-Guillamon M, Pruzin J, Sperling R, van Veluw SJ. Cerebral amyloid angiopathy and Alzheimer disease — one peptide, two pathways. Nat Rev Neurol. 2020;16:30–42.

Article  CAS  PubMed  Google Scholar 

Pfeifer LA, White LR, Ross GW, Petrovitch H, Launer LJ. Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study. Neurology. 2002;58:1629–34.

Article  CAS  PubMed  Google Scholar 

Case NF, Charlton A, Zwiers A, Batool S, McCreary CR, Hogan DB, Ismail Z, Zerna C, Coutts SB, Frayne R, Goodyear B, Haffenden A, Smith EE. Cerebral amyloid angiopathy is associated with executive dysfunction and mild cognitive impairment. Stroke. 2016;47:2010–6.

Article  PubMed  Google Scholar 

Attems J, Jellinger K, Thal DR, Van Nostrand W. Review: Sporadic cerebral amyloid angiopathy. Neuropathol Appl Neurobiol. 2011;37:75–93.

Article  CAS  PubMed  Google Scholar 

Zipfel GJ, Han H, Ford AL, Lee JM. Cerebral amyloid angiopathy progressive disruption of the neurovascular unit. Stroke. 2009;40:S16–9.

Article  PubMed  Google Scholar 

Han BH, Zhou ML, Abousaleh F, Brendza RP, Dietrich HH, Koenigsknecht-Talboo J, Cirrito JR, Milner E, Holtzman DM, Zipfel GJ. Cerebrovascular dysfunction in amyloid precursor protein transgenic mice: Contribution of soluble and insoluble amyloid-β peptide, partial restoration via γ-secretase inhibition. J Neurosci. 2008;28:13542–50.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Weller RO, Subash M, Preston SD, Mazanti I, Carare RO. Perivascular drainage of amyloid-β peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer’s disease. Brain Pathol. 2008;18:253–66.

Article  CAS  PubMed  Google Scholar 

Liao F, Yoon H, Kim J. Apolipoprotein E metabolism and functions in brain and its role in Alzheimerʼs disease. Curr Opin Lipidol. 2016;28:60–7.

Article  Google Scholar 

Nelson P. T., Pious N. M., Jicha G. A., Wilcock D. M., Fardo D. W., Fardo S, Estus G, Rebeck G. William. APOE-ε2 and APOE ε4 correlate with increased amyloid accumulation in cerebral vasculature. J Neuropathol Exp Neurol. 2013;72:708–15.

Article  CAS  PubMed  Google Scholar 

Greenberg SM, Briggs ME, Hyman BT, Kokoris GJ, Takis C, Kanter DS, et al. Apolipoprotein E ε4 is associated with the presence and earlier onset of hemorrhage in cerebral amyloid angiopathy. Stroke. 1996;27:1333–7.

Fryer JD, Simmons K, Parsadanian M, Bales KR, Paul SM, Sullivan PM, Holtzman DM. Human apolipoprotein E4 alters the amyloid-β 40:42 ratio and promotes the formation of cerebral amyloid angiopathy in an amyloid precursor protein transgenic model. J Neurosci. 2005;25:2803–10.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ringman JM, Sachs MC, Zhou Y, Monsell SE, Saver JL, Vinters HV. Clinical predictors of severe cerebral amyloid angiopathy and influence of APOE genotype in persons with pathologically verified Alzheimer disease. JAMA Neurol. 2014;71:878–83.

Article  PubMed  PubMed Central  Google Scholar 

Strittmatter W. J., Saunders A. M., Schmechel D., Pericak-Vance M., Enghild J., Salvesen G. S., Roses A. D. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A. 1993;90:1977–81.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu C-C, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013;9:106–18.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Castellano J. M., Kim J., Stewart F. R., Jiang H., DeMattos R. B., Patterson B. W., Fagan A. M., Morris J. C., Mawuenyega K. G., Cruchaga C., Goate A. M., Bales K. R., Paul S. M., Bateman R. J., Holtzman D. M. Human apoE Isoforms Differentially Regulate Brain Amyloid-beta Peptide Clearance. Sci Transl Med. 2011;3:89ra57.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martens YA, Zhao N, Liu CC, Kanekiyo T, Yang AJ, Goate AM, Holtzman DM, Bu G. ApoE Cascade Hypothesis in the pathogenesis of Alzheimer’s disease and related dementias. Neuron. 2022;110:1304–17.

Article  CAS  PubMed  Google Scholar 

Hawkes CA, Härtig W, Kacza J, Schliebs R, Weller RO, Nicoll JA, Carare RO. Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy. Acta Neuropathol. 2011;121:431–43.

Article  PubMed  Google Scholar 

Herzig M. C., Nostrand W. E. Van, Jucker M. Mechanism of cerebral beta-amyloid angiopathy: murine and cellular models. Brain Pathol. 2006;16:40–54.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Verbeek MM, Otte-Höller I, Veerhuis R, Ruiter DJ, De Waal RMW. Distribution of Aβ-associated proteins in cerebrovascular amyloid of Alzheimer’s disease. Acta Neuropathol. 1998;96:628–36.

Article  CAS  PubMed  Google Scholar 

Namba K., Tomonaga M, Kawasaki H, Otomo E, Ikeda. Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer’s disease and kuru plaque amyloid in Creutzfeldt-Jakob disease. Brain Res. 1991;541:163–6.

Article  CAS  PubMed  Google Scholar 

Wisniewski T, Frangione B. Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid. Neurosci Lett. 1992;135:235–8.

Article  CAS  PubMed  Google Scholar 

Fryer J. D., Taylor J. W., DeMattos R. B., Bales K. R., Paul S. M., Parsadanian M., Holtzman D. M. Apolipoprotein E markedly facilitates age-dependent cerebral amyloid angiopathy and spontaneous hemorrhage in amyloid precursor protein transgenic mice. J Neurosci. 2003;23:7889–96.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Holtzman DM, Fagan AM, Mackey B, Tenkova T, Sartorius L, Paul SM, Bales K, Ashe KH, Irizarry MC, Hyman BT. Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer’s disease model. Ann Neurol. 2000;47:739–47.

Article  CAS  PubMed  Google Scholar 

Caselli RJ, Dueck AC, Locke DEC, Hoffman-Snyder CR, Woodruff BK, Rapcsak SZ, Reiman EM. Longitudinal modeling of frontal cognition in APOE ε4 homozygotes, heterozygotes, and noncarriers. Neurology. 2011;76:1383–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wierenga CE, Dev SI, Shin DD, Clark LR, Bangen KJ, Jak AJ, Rissman RA, Liu TT, Salmon DP, Bondi MW. Effect of mild cognitive impairment and APOE genotype on resting cerebral blood flow and its association with cognition. J Cereb Blood Flow Metab. 2012;32:1589–99.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kisler K, Nelson AR, Montagne A, Zlokovic BV. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat Rev Neurosci. 2017;18:419–34.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tai LM, Thomas R, Marottoli FM, Koster KP, Kanekiyo T, Morris AWJ, Bu G. The role of APOE in cerebrovascular dysfunction. Acta Neuropathol. 2016;131:709–23.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Montagne A., Nation D. A., Sagare A. P., Barisano G., Sweeney M. D., Chakhoyan A., Pachicano M., Joe E., Nelson A. R., D’Orazio L. M., Buennagel D. P., Harrington M. G., Benzinger T. L. S., Fagan A. M., Ringman J. M., Schneider L. S., Morris J. C., Reiman E. M., Caselli R. J., Chui H. C., TCW J., Chen Y., Pa J., Conti P. S., Law M., Toga A. W., Zlokovic B. V. APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline. Nature. 2020;581:71–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bell RD, Winkler EA, Singh I, Sagare AP, Deane R, Wu Z, Holtzman DM, Betsholtz C, Armulik A, Sallstrom J, Berk BC, Zlokovic BV. Apolipoprotein e controls cerebrovascular integrity via cyclophilin A. Nature. 2012;485:512–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, Dvir-Szternfeld R, Ulland TK, David E, Baruch K, Lara-Astaiso D, Toth B, Itzkovitz S, Colonna M, Schwartz M, Amit I. A unique microglia type associated with restricting development of alzheimer’s disease. Cell. 2017;169:1276-1290.e17.

Article  CAS  PubMed