Gorelick, P. B. et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42, 2672–2713 (2011). An overall guide for practitioners to gain a better understanding of VCID.

Article  PubMed  PubMed Central  Google Scholar 

Kalaria, R. N. & Ballard, C. Overlap between pathology of Alzheimer disease and vascular dementia. Alzheimer Dis. Assoc. Disord. 13, S115–S123 (1999).

Article  PubMed  Google Scholar 

Iadecola, C. et al. Vascular cognitive impairment and dementia: JACC Scientific Expert Panel. J. Am. Coll. Cardiol. 73, 3326–3344 (2019). A critical appraisal of the epidemiology, pathobiology, neuropathology and neuroimaging of VCID.

Article  PubMed  PubMed Central  Google Scholar 

Simrén, J. et al. The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer’s disease. Alzheimers Dement. 17, 1145–1156 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Jack, C. R. Jr. et al. NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 14, 535–562 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Iadecola, C. The pathobiology of vascular dementia. Neuron 80, 844–866 (2013). A review of the pathophysiology of VCID.

Article  CAS  PubMed  Google Scholar 

van der Flier, W. M. et al. Vascular cognitive impairment. Nat. Rev. Dis. Prim. 4, 18003 (2018). A comprehensive review of VCID.

Article  PubMed  Google Scholar 

Zhou, X. J., Vaziri, N. D., Wang, X. Q., Silva, F. G. & Laszik, Z. Nitric oxide synthase expression in hypertension induced by inhibition of glutathione synthase. J. Pharmacol. Exp. Ther. 300, 762–767 (2002).

Article  CAS  PubMed  Google Scholar 

Dowsett, L. et al. ADMA: a key player in the relationship between vascular dysfunction and inflammation in atherosclerosis. J. Clin. Med. 9, 3026 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Iadecola, C. & Gottesman, R. F. Neurovascular and cognitive dysfunction in hypertension. Circ. Res. 124, 1025–1044 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Iadecola, C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron 96, 17–42 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kernagis, D. N. & Laskowitz, D. T. Evolving role of biomarkers in acute cerebrovascular disease. Ann. Neurol. 71, 289–303 (2012).

Article  CAS  PubMed  Google Scholar 

Faraco, G. et al. Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nat. Neurosci. 21, 240–249 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Faraco, G. et al. Dietary salt promotes cognitive impairment through tau phosphorylation. Nature 574, 686–690 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shimokawa, H. & Godo, S. Nitric oxide and endothelium-dependent hyperpolarization mediated by hydrogen peroxide in health and disease. Basic Clin. Pharmacol. Toxicol. 127, 92–101 (2020).

Article  CAS  PubMed  Google Scholar 

Zlokovic, B. V. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat. Rev. Neurosci. 12, 723–738 (2011). A review of pathophysiology of the neurovascular unit.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sweeney, M. D., Sagare, A. P. & Zlokovic, B. V. Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat. Rev. Neurol. 14, 133–150 (2018). A review of the blood–brain barrier in Alzheimer disease and other neurodegenerative disorders.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nation, D. A. et al. Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat. Med. 25, 270–276 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sweeney, M. D. et al. A novel sensitive assay for detection of a biomarker of pericyte injury in cerebrospinal fluid. Alzheimers Dement. 16, 821–830 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Rosenberg, G. A. Willis lecture: biomarkers for inflammatory white matter injury in Binswanger disease provide pathways to precision medicine. Stroke 53, 3514–3523 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Nikolakopoulou, A. M. et al. Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss. Nat. Neurosci. 22, 1089–1098 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Procter, T. V., Williams, A. & Montagne, A. Interplay between brain pericytes and endothelial cells in dementia. Am. J. Pathol. 191, 1917–1931 (2021).

Article  CAS  PubMed  Google Scholar 

Armulik, A. et al. Pericytes regulate the blood-brain barrier. Nature 468, 557–561 (2010).

Article  CAS  PubMed  Google Scholar 

Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C. & Gage, F. H. Mechanisms underlying inflammation in neurodegeneration. Cell 140, 918–934 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Touyz, R. M. & Briones, A. M. Reactive oxygen species and vascular biology: implications in human hypertension. Hypertens. Res. 34, 5–14 (2011).

Article  CAS  PubMed  Google Scholar 

Mayhan, W. G., Arrick, D. M., Sharpe, G. M. & Sun, H. Age-related alterations in reactivity of cerebral arterioles: role of oxidative stress. Microcirculation 15, 225–236 (2008).

Article  CAS  PubMed  Google Scholar 

Dong, Y. F. et al. Attenuation of brain damage and cognitive impairment by direct renin inhibition in mice with chronic cerebral hypoperfusion. Hypertension 58, 635–642 (2011).

Article  CAS  PubMed  Google Scholar 

Santhanam, A. V., d’Uscio, L. V. & Katusic, Z. S. Erythropoietin increases bioavailability of tetrahydrobiopterin and protects cerebral microvasculature against oxidative stress induced by eNOS uncoupling. J. Neurochem. 131, 521–529 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Prasad, K. AGE-RAGE stress: a changing landscape in pathology and treatment of Alzheimer’s disease. Mol. Cell Biochem. 459, 95–112 (2019).

Article  CAS  PubMed  Google Scholar 

Tang, Y. & Le, W. Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol. Neurobiol. 53, 1181–1194 (2016).

Article  CAS  PubMed  Google Scholar 

Guo, S., Wang, H. & Yin, Y. Microglia polarization from M1 to M2 in neurodegenerative diseases. Front. Aging Neurosci. 14, 815347 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim, E., Otgontenger, U., Jamsranjav, A. & Kim, S. S. Deleterious alteration of glia in the brain of Alzheimer’s disease. Int. J. Mol. Sci. 21, 6676 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen, B., Cheng, Q., Yang, K. & Lyden, P. D. Thrombin mediates severe neurovascular injury during ischemia. Stroke 41, 2348–2352 (2010).

Article  CAS  PubMed  Google Scholar 

Zoia, A., Drigo, M., Caldin, M., Simioni, P. & Piek, C. J. Fibrinolysis in dogs with intracavitary effusion: a review. Animals 12, 2487 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Chen, Z. L. & Strickland, S. Neuronal death in the hippocampus is promoted by plasmin-catalyzed degradation of laminin. Cell 91, 917–925 (1997).

Article  CAS  PubMed  Google Scholar 

Ihara, M. et al. Chronic cerebral hypoperfusion induces MMP-2 but not MMP-9 expression in the microglia and vascular endothelium of white matter. J. Cereb. Blood Flow Metab. 21, 828–834 (2001).

Article  CAS  PubMed  Google Scholar