Cerebral Arterial Wall Research Articles

3-Aminobenzamide protects against cerebral artery injury and inflammation in rats with intracranial aneurysms.

This study aimed to investigate the treatment effects and molecular mechanism of 3-aminobenzamide (3-AB) on intracranial aneurysms (IA). The IA model was established in male Sprague-Dawley (SD) rats and sham group was set up without ligation. The rats were intraperitoneally injected with normal saline in sham and model control groups and 10 mg/kg, 20 mg/kg and 40 mg/kg 3-AB for low, middle and high 3-AB groups for 3 months, respectively. The rates in and blood pressures of caudal artery were measured and anterior cerebral artery and olfactory artery were stained with hematoxylin and eosin (HE) for morphology observation. Besides, the effects of 3-AB on inflammatory cells, macrophages, neutrophils and T cells, were evaluated using immunohistochemistry. Gene expressions of TNF-α, MMP-9, MMP-2, iNOS, TLR4, PARP-1 and p65 were measured using qRT-PCR and the protein levels of TLR4, PARP-1 and p-p65 were evaluated using western blotting. Blood pressures of rats in 3-AB treatment groups were decreased in a dose-dependent manner. The damage of cerebral artery wall was alleviated and the inflammatory cells (macrophages, neutrophils and T cells) were reduced to some extent in 3-AB high-dose groups. The gene expression of TNF-α, MMP-9, MMP-2, iNOS, TLR4, PARP-1 and p65, as well as the protein expression of TLR4, PARP-1 and p-p65 in 3-AB treatment groups were decreased in a dose-dependent manner (P < 0.01).3-AB exhibited therapeutic effects on IA through inhibiting the secretions of inflammatory cytokines and MMPs.

Features of the Structure of Cerebral Vessels in Persons who Died from Rupture of Cerebral Artery Aneurysm

The aimof the study is to define of variants of the Willi’s circle and also structural features of the vessel walls at the site of aneurysm location in people who died from aneurysms in the dead from their rupture to identify risk groups for cerebrovascular disease.Material and methods.The structure of cerebral vessels of 8 people at the age from 17 to 69 of both sexes who died from subarachnoid hemorrhage of aneurysmal genesis was examined due to macro-microscopical and clinical methods. Histology slides of cerebral arterial walls of aneurysm area were stained with hematoxylin-eosin and Mallory’s technique and then were examined.Results. Variants of the Willi’s circle and morphological features of vessel walls located in aneurysm formation area in people who died from aneurysm rupture are shown in the articleConclusion. Not classic variants of Willi’s circle, fibromuscular dysplasia of the medial type and atherosclerotic changes of vessel walls contributes to aneurysm occurrence in cerebral vessels.

Anti-vasospastic Effects of Epidermal Growth Factor Receptor Inhibitors After Subarachnoid Hemorrhage in Mice.

Subarachnoid hemorrhage (SAH) is a devastating disease. Cerebral vasospasm is still an important cause of post-SAH poor outcomes, but its mechanisms remain unveiled. Activation of epidermal growth factor receptor (EGFR) is suggested to cause vasoconstriction in vitro, but no report has demonstrated the involvement of EGFR in vasospasm development after SAH in vivo. Cross-talk of EGFR and vascular endothelial growth factor (VEGF) receptor, which may affect post-SAH vasospasm, was also reported in cancer cells, but has not been demonstrated in post-SAH vasospasm. The aim of this study was to investigate whether EGFR as well as EGFR-VEGF receptor cross-talk engage in the development of cerebral vasospasm in a mouse SAH model. C57BL6 mice underwent endovascular perforation SAH or sham modeling. At 30min post-modeling, mice were randomly administrated vehicle or 2 doses of selective EGFR inhibitors intracerebroventricularly. A higher dose of the inhibitor significantly prevented post-SAH neurological impairments at 72h and vasospasm at 24h associated with suppression of post-SAH activation of EGFR and extracellular signal-regulated kinase (ERK) 1/2 in the cerebral artery wall, especially in the smooth muscle cell layers. Anti-EGFR neutralizing antibody also showed similar effects. However, neither expression levels of VEGF nor activation levels of a major receptor of VEGF, VEGF receptor-2, were affected by SAH and two kinds of EGFR inactivation. Thus, this study first showed that EGFR-ERK1/2 pathways may be involved in post-SAH vasospasm development, and that EGFR-VEGF receptor cross-talk may not play a significant role in the development of vasospasm in mice.

Application of High-Resolution CUBE Sequence in Exploring Stroke Mechanisms of Atherosclerotic Stenosis of Middle Cerebral Artery

BackgroundThis study aimed to analyze the vascular wall and atherosclerotic plaques of the middle cerebral artery (MCA) and compare their differences between patients with cerebral infarction and transient ischemic attack (TIA) using 3-dimensional fast-spin-echo T1-weighted sequence (namely CUBE). MethodsForty-seven patients with atherosclerotic stenosis of the MCA were included in this study. They received magnetic resonance examinations with routine T1WI, T2WI, 3-dimensional time-of-flight magnetic resonance angiography and diffusion-weighted imaging, as well as high-resolution CUBE T1WI sequence. Two physicians independently observed the location and degree of enhancement of the atheromatous plaques. The vessel area and lumen area at the maximal-lumen-narrowing and reference site were measured to calculate the plaque area, rate of stenosis, and remodeling index of the MCA. The chi-squared test was used to compare the differences of degree of enhancement between the cerebral infarction and TIA groups. The differences of rate of stenosis and remodeling index were compared by independent sample t test. ResultsTwenty-five lesion vessels in the infarction group and 22 in the TIA group were analyzed. The difference of stenosis rate between the groups was not statistically significant. The lesion vessels of infarction group had a significantly larger remodeling index and plaque area, and the plaques had a significantly higher degree of enhancement, compared to the TIA group. ConclusionsCUBE T1WI can be used to characterize the MCA vessel wall and atherosclerotic plaque. Positive remodeling and enhanced plaques are closely correlated with the occurrence of brain stroke.

Selection of Flow-Diverter Stent Models Using Optical Coherence Tomography and Mathematical Modeling of Hemodynamics

We describe a method for increasing the effectiveness of surgery to position flow-diverter stents into cerebral arteries with aneurysms based on the combined use of mathematical modeling of hemodynamics and compression elastography. Approaches to determining Young's modulus and the Poisson's ratio for phantom of cerebral artery walls on the basis of endoscopic optical coherence tomography data were developed and tested. The applicability of this method was verified using a model of internal carotid artery aneurysm using a mathematical hemodynamic model taking into account the mechanical properties of the cerebral artery wall.

Extracranial arterial wall volume is increased and shows relationships with vascular MRI measures in idiopathic Parkinson’s disease

ObjectiveIdiopathic Parkinson’s disease (IPD) is the second most common neurodegenerative disorder, often complicated by dementia. Cardiovascular risk factors and spontaneous cerebral emboli (SCE) are strongly associated with Alzheimer’s (AD) and vascular dementia (VaD). We measured SCE in the middle cerebral artery and arterial wall volume in the extracranial arteries in patients with IPD and controls, and explored the relationships with structural and physiological MRI brain neurovascular measures. Patients and MethodsArterial wall volume over 2cm of the axillary and internal carotid arteries (ICA) bilaterally was measured by 3-D tomographic ultrasound in 15 IPD patients and 16 age/gender matched controls. SCE were counted by Transcranial Doppler (TCD) using international consensus criteria. Venous to arterial circulation shunting (v-aCS), usually through a patent foramen ovale (PFO), was measured using a TCD technique with intravenous microbubble contrast. Structural and physiological MRI brain neurovascular measures, acquired separately, comprised white matter lesion volume (WMLV), cerebral blood flow (CBF) and arterial arrival time (AAT). ResultsMean (95% CI) axillary and ICA wall volume was higher in IPD patients at 523 mm3 (446, 600) and 455 mm3 (374, 536) respectively compared with 412 mm3 (342, 483) and 408 mm3 (362, 454) in controls being significant for the axillary artery (p = 0.04).Cerebral WMLV was related to mean arterial wall volume for both axillary (r = 0.555, p = 0.009) and ICA (r = 0.559, p = 0.026) in all participants.SCE were detected in four IPD patients and three controls (p = 1.00). Two IPD patients and three controls were positive for a v-aCS equivalent to PFO (p = 0.477). ConclusionAlthough frequent in AD and VaD, neither SCE nor v-aCS were associated with IPD. This is the first study to demonstrate arterial wall volume is increased in IPD and relates to WMLV.

Role of Perinatal Inflammation in Neonatal Arterial Ischemic Stroke.

Based on the review of the literature, perinatal inflammation often induced by infection is the only consistent independent risk factor of neonatal arterial ischemic stroke (NAIS). Preclinical studies show that acute inflammatory processes take place in placenta, cerebral arterial wall of NAIS-susceptible arteries and neonatal brain. A top research priority in NAIS is to further characterize the nature and spatiotemporal features of the inflammatory processes involved in multiple levels of the pathophysiology of NAIS, to adequately design randomized control trials using targeted anti-inflammatory vasculo- and neuroprotective agents.

Abstract P441: Accelerated Age-dependent Cardiovascular and Cognitive Decline in Dahl-S Rats is Associated with Elevated Levels of an Endogenous Na/K-ATPase Inhibitor

Age-associated central arterial stiffening contributes to both cerebral arterial fibrosis and to cognitive impairment. Accelerated aging, accompanied by a gradual increase in blood pressure (BP) and aortic remodeling, occurs in Dahl-S rats (DSS) vs. normotensive Sprague-Dawley rats (S-D) counterparts even in the absence of a high salt intake. A novel pro-hypertensive factor marinobufagenin (MBG) is implicated in DSS hypertension. Here we determined whether an increase in MBG is also implicated in age-associated arterial remodeling in DSS. Methods: Life span was measured in 60 S-D and 78 DSS. BP, pulse wave velocity (PWV), behavioral water maze test, ANGII, MBG and aortic collagen were assessed in 3 and 9-mo S-D and DSS on a normal 0.5% NaCl intake. Results: Median life span in DSS is reduced by 50% vs. S-D (12±1 vs. 24±2 mo, p&lt;0.01). At 3-mo DSS had higher SBP, PWV, ANGII, MBG, aortic and large cerebral arterial wall remodeling vs. 3-mo S-D (Table). Between 3 and 9-mo DSS, but not S-D, exhibited further increase in SBP, PWV, MBG and aortic collagen deposition. In a redundant place-cue version of the water maze test, 3-mo DSS demonstrated numerically impaired spatial hippocampal memory vs. 3-mo S-D, and by 9-mo, performance in DSS suggested the development of motor impairments, thus precluding an uncontaminated assessment of their spatial memory. Conclusions: In DSS high MBG occurred concurrently with fibrosis of aorta and large cerebral arteries and numerically impaired spatial memory. With advancing age of DSS further increase in BP, aortic stiffness and spatial learning/motor deficit occurred in context with an increase in MBG, which suggested an implication of MBG in these declines.

Macrophage Imaging of Cerebral Aneurysms with Ferumoxytol: an Exploratory Study in an Animal Model and in Patients

The purpose of this study is to assess the validity and feasibility of macrophage imaging using an ultrasmall superparamagnetic iron oxide nanoparticle, ferumoxytol, in the cerebral aneurysmal wall in an animal model and in humans. Engulfment of ferumoxytol by primary culture of macrophages and RAW264.7 cells was assessed. Uptake of ferumoxytol was evaluated histologically in a cerebral aneurysmal model in rats. In an exploratory clinical study of magnetic resonance macrophage imaging, 17 unruptured aneurysms in 17 patients were imaged using thin-slice gapless magnetic resonance images of 2D-gradient-recalled echo (2D-GRE) and 3D-T1-fast-spin echo sequences on day 0 and of the same sequences with infusion of ferumoxytol 24 hours after the first imaging. Pre- and postinfusion images were evaluated independently by 2 medical doctors. Engulfment of ferumoxytol was confirmed in vitro, but the amount of ferumoxytol uptake was independent of the activation state or the differentiation state. Ferumoxytol uptake in CD68-positive cells was observed in the cerebral arterial walls of 4 out of 15 (26.7%) experimentally induced aneurysms in rats. In a clinical study, 17 aneurysms were enrolled and 2 aneurysms were not assessed because of incomplete images. Eleven aneurysms without oral intake of recent anti-inflammatory agents of the remaining 15 aneurysms showed ferumoxytol uptake on 2D-GRE subtraction images, and the size of the aneurysms was significantly related to positive images. Ferumoxytol uptake was confirmed in cultured macrophages and in the cerebral aneurysmal wall in rats. Thin-slice gapless magnetic resonance imaging with ferumoxytol in human cerebral aneurysmal walls may reflect macrophages in the cerebral aneurysmal wall, but its application to small-sized lesions may be restricted.

Immunolocation of Heme Oxygenases in the Walls of Cerebral Arteries of Various Diameters in Rats.

The distribution of two enzymes involved in the formation of carbon monoxide, heme oxygenases 1 and 2, in the pial branches of orders I-V of the middle cerebral artery basin and in intracerebral vessels was studied in adult Wistar rats. Immunohistochemical studies detected hemeoxygenase-2 in the endothelium of the small pial and intracerebral arterioles and in myocytes of pial branches I-III. Heme oxygenase 1, an inducible form of the enzyme, is normally not expressed in the cerebral vessels, but the enzyme is expressed in response to sodium metaarsenite. In this case, heme oxygenase markers are detected in myocytes of pial arteries I-II and in the endothelium of small pial and intracerebral vessels. Sodium meta-arsenite is inessential for immunolocation and quantitative distribution of heme oxygenase 2 in the vessels.

Assessment of Arterial Wall Enhancement for Differentiation of Parent Artery Disease from Small Artery Disease: Comparison between Histogram Analysis and Visual Analysis on 3-Dimensional Contrast-Enhanced T1-Weighted Turbo Spin Echo MR Images at 3T

ObjectiveThe purpose of this study was to compare the histogram analysis and visual scores in 3T MRI assessment of middle cerebral arterial wall enhancement in patients with acute stroke, for the differentiation of parent artery disease (PAD) from small artery disease (SAD).Materials and MethodsAmong the 82 consecutive patients in a tertiary hospital for one year, 25 patients with acute infarcts in middle cerebral artery (MCA) territory were included in this study including 15 patients with PAD and 10 patients with SAD. Three-dimensional contrast-enhanced T1-weighted turbo spin echo MR images with black-blood preparation at 3T were analyzed both qualitatively and quantitatively. The degree of MCA stenosis, and visual and histogram assessments on MCA wall enhancement were evaluated. A statistical analysis was performed to compare diagnostic accuracy between qualitative and quantitative metrics.ResultsThe degree of stenosis, visual enhancement score, geometric mean (GM), and the 90th percentile (90P) value from the histogram analysis were significantly higher in PAD than in SAD (p = 0.006 for stenosis, < 0.001 for others). The receiver operating characteristic curve area of GM and 90P were 1 (95% confidence interval [CI], 0.86–1.00).ConclusionA histogram analysis of a relevant arterial wall enhancement allows differentiation between PAD and SAD in patients with acute stroke within the MCA territory.

Regression of atherosclecrotic lesions: medicinal and alimentary factors

The article reports results of clinical studies aimed to elucidate the influence of medicines on the size and density of atherosclerotic plaques in the walls of coronary and cerebral arteries. The phenomenon of regression of atherosclerotic lesions in the survivors of Leningrad siege during a long period of starvation is analyzed. The influence of inhibitors of angiotensin-converting enzyme on apoptosis of smooth muscle and foam cells of atherosclerotic plaques in the sanological mechanisms of atherosclerosis is discussed. The concept of natural regression of atherosclerosis is formulated and the necessity of development of the methods for is pharmacological activation are formulated.

Virtual Inflation of the Cerebral Artery Wall for the Integrated Exploration of OCT and Histology Data

AbstractIntravascular imaging provides new insights into the condition of vessel walls. This is crucial for cerebrovascular diseases including stroke and cerebral aneurysms, where it may present an important factor for indication of therapy. In this work, we provide new information of cerebral artery walls by combining ex vivo optical coherence tomography (OCT) imaging with histology data sets. To overcome the obstacles of deflated and collapsed vessels due to the missing blood pressure, the lack of co‐alignment as well as the geometrical shape deformations due to catheter probing, we developed the new image processing method virtual inflation. We locally sample the vessel wall thickness based on the (deflated) vessel lumen border instead of the vessel's centerline. Our method is embedded in a multi‐view framework where correspondences between OCT and histology can be highlighted via brushing and linking yielding OCT signal characteristics of the cerebral artery wall and its pathologies. Finally, we enrich the data views with a hierarchical clustering representation which is linked via virtual inflation and further supports the deduction of vessel wall pathologies.

Vascular, glial, and lymphatic immune gateways of the central nervous system.

Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood–brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system. Recent developments in high-resolution imaging techniques have prompted a reassessment of the relationships between the CNS and the immune system. This review will take these developments into account in describing our present understanding of the anatomical connections of the CNS fluid drainage pathways towards regional lymph nodes and our current concept of immune cell trafficking into the CNS during immunosurveillance and neuroinflammation. Cerebrospinal fluid (CSF) and interstitial fluid are the two major components that drain from the CNS to regional lymph nodes. CSF drains via lymphatic vessels and appears to carry antigen-presenting cells. Interstitial fluid from the CNS parenchyma, on the other hand, drains to lymph nodes via narrow and restricted basement membrane pathways within the walls of cerebral capillaries and arteries that do not allow traffic of antigen-presenting cells. Lymphocytes targeting the CNS enter by a two-step process entailing receptor-mediated crossing of vascular endothelium and enzyme-mediated penetration of the glia limitans that covers the CNS. The contribution of the pathways into and out of the CNS as initiators or contributors to neurological disorders, such as multiple sclerosis and Alzheimer’s disease, will be discussed. Furthermore, we propose a clear nomenclature allowing improved precision when describing the CNS-specific communication pathways with the immune system.

Influence of Low-Dose Aspirin on Cerebral Amyloid Angiopathy in Mice.

Accumulation of amyloid-β peptide (Aβ) in the brain is one of the most important features of Alzheimer's dementia (AD). Cerebral amyloid angiopathy (CAA) is characterized by Aβ accumulation in the walls of cerebral arteries and capillaries, and is present in over 90% of patients with AD. Several novel agents for AD/CAA developed around the amyloid hypothesis have shown positive signs in animal studies but have failed in clinical trials due to adverse events and/or lack of efficiency. As CAA is presumably caused by a failure in Aβ clearance, drugs that promote Aβ clearance may hold promise in the treatment of CAA and possibly AD. With this in mind, cilostazol, an anti-platelet drug with vasodilating action, has been found to promote Aβ clearance along perivascular drainage pathway, reduce Aβ accumulation in the brain, and restore memory impairment in Tg-SwDI mice, an animal model of CAA. We therefore tested whether the most common anti-platelet agent, aspirin, also reduced Aβ and rescued cognitive impairment in Tg-SwDI mice, and also whether aspirin affected hemorrhagic complications that can occur in Tg-SwDI mice. Mice aged 4 months were assigned into vehicle-treated and low-dose aspirin-treated groups. Low-dose aspirin for 8 months did not increase hemorrhagic lesions, nor increase resting cerebral blood flow or cerebral vascular reserve in response to hypercapnia or acetylcholine. Subsequently, aspirin did not restore cognitive dysfunction. These results suggest that low-dose aspirin does not have a direct influence on cerebrovascular Aβ metabolism nor aggravate hemorrhagic complications in CAA.

A Simulation Model of Periarterial Clearance of Amyloid-β from the Brain

The accumulation of soluble and insoluble amyloid-β (Aβ) in the brain indicates failure of elimination of Aβ from the brain with age and Alzheimer's disease (AD). There is a variety of mechanisms for elimination of Aβ from the brain. They include the action of microglia and enzymes together with receptor-mediated absorption of Aβ into the blood and periarterial lymphatic drainage of Aβ. Although the brain possesses no conventional lymphatics, experimental studies have shown that fluid and solutes, such as Aβ, are eliminated from the brain along 100 nm wide basement membranes in the walls of cerebral capillaries and arteries. This lymphatic drainage pathway is reflected in the deposition of Aβ in the walls of human arteries with age and AD as cerebral amyloid angiopathy (CAA). Initially, Aβ diffuses through the extracellular spaces of gray matter in the brain and then enters basement membranes in capillaries and arteries to flow out of the brain. Although diffusion through the extracellular spaces of the brain has been well characterized, the exact mechanism whereby perivascular elimination of Aβ occurs has not been resolved. Here we use a computational model to describe the process of periarterial drainage in the context of diffusion in the brain, demonstrating that periarterial drainage along basement membranes is very rapid compared with diffusion. Our results are a validation of experimental data and are significant in the context of failure of periarterial drainage as a mechanism underlying the pathogenesis of AD as well as complications associated with its immunotherapy.

Characteristics of time-varying intracranial pressure on blood flow through cerebral artery: A fluid-structure interaction approach.

Elevated intracranial pressure is a major contributor to morbidity and mortality in severe head injuries. Wall shear stresses in the artery can be affected by increased intracranial pressures and may lead to the formation of cerebral aneurysms. Earlier research on cerebral arteries and aneurysms involves using constant mean intracranial pressure values. Recent advancements in intracranial pressure monitoring techniques have led to measurement of the intracranial pressure waveform. By incorporating a time-varying intracranial pressure waveform in place of constant intracranial pressures in the analysis of cerebral arteries helps in understanding their effects on arterial deformation and wall shear stress. To date, such a robust computational study on the effect of increasing intracranial pressures on the cerebral arterial wall has not been attempted to the best of our knowledge. In this work, fully coupled fluid-structure interaction simulations are carried out to investigate the effect of the variation in intracranial pressure waveforms on the cerebral arterial wall. Three different time-varying intracranial pressure waveforms and three constant intracranial pressure profiles acting on the cerebral arterial wall are analyzed and compared with specified inlet velocity and outlet pressure conditions. It has been found that the arterial wall experiences deformation depending on the time-varying intracranial pressure waveforms, while the wall shear stress changes at peak systole for all the intracranial pressure profiles.

Peristalsis with Oscillating Flow Resistance: A Mechanism for Periarterial Clearance of Amyloid Beta from the Brain.

Alzheimer's disease is characterized by accumulation of amyloid-β (Aβ) in the brain and in the walls of cerebral arteries. The focus of this work is on clearance of Aβ along artery walls, the failure of which may explain the accumulation of Aβ in Alzheimer's disease. Periarterial basement membranes form continuous channels from cerebral capillaries to major arteries on the surface of the brain. Arterial pressure pulses drive peristaltic flow in the basement membranes in the same direction as blood flow. Here we forward the hypothesis that flexible structures within the basement membrane, if oriented such they present greater resistance to forward than retrograde flow, may cause net reverse flow, advecting Aβ along with it. A solution was obtained for peristaltic flow with low Reynolds number, long wavelength compared to channel height and small channel height compared to vessel radius in a Darcy-Brinkman medium representing a square array of cylinders. Results show that retrograde flow is promoted by high cylinder volume fraction and low peristaltic amplitude. A decrease in cylinder concentration and/or an increase in amplitude, both of which may occur during ageing, can reduce retrograde flow or even cause a transition from retrograde to forward flow. Such changes may explain the accumulation of Aβ in the brain and in artery walls in Alzheimer's disease.

Transient Cerebral Arteriopathy in a Child Associated With Cytomegalovirus Infection.

Vascular wall injuries account for up to 80% of childhood strokes, excluding emboli of cardiac origin. Transient cerebral arteriopathy is a recently described entity that is increasingly recognized as an important cause. The cerebral arterial wall is thought to be affected by an inflammatory process related to certain infections. The authors report a 2.5-year-old girl with sudden left hemiplegia and aphasia. The neuroimaging showed occlusion of the right middle cerebral artery and ischemic damages. Laboratory revealed positive cytomegalovirus immunoglobulin M and G in cerebrospinal fluid and in early and late sera. Treatment with ganciclovir, anticytomegalovirus immunoglobulin, and prednisolone, followed by oral aspirin, resulted in clinical improvement. The follow-up neuroimaging showed stabilization of the arterial lesions without residual stenosis. To our knowledge, this is the first report of a cytomegalovirus-associated transient cerebral arteriopathy in an immunocompetent child. Our report demonstrates the propensity for cytomegalovirus to be involved in pediatric cerebral vascular disease.

Quantification of molecular interactions between ApoE, amyloid-beta (Aβ) and laminin: Relevance to accumulation of Aβ in Alzheimer's disease

Accumulation of amyloid-β (Aβ) in plaques in the brain and in artery walls as cerebral amyloid angiopathy indicates a failure of elimination of Aβ from the brain with age and Alzheimer's disease. A major pathway for elimination of Aβ and other soluble metabolites from the brain is along basement membranes within the walls of cerebral arteries that represent the lymphatic drainage pathways for the brain. The motive force for the elimination of Aβ along this perivascular pathway appears to be the contrary (reflection) wave that follows the arterial pulse wave. Following injection into brain parenchyma, Aβ rapidly drains out of the brain along basement membranes in the walls of cerebral arteries; such drainage is impaired in apolipoprotein E ε4 (ApoE4) mice. For drainage of Aβ to occur in a direction contrary to the pulse wave, some form of attachment to basement membrane would be required to prevent reflux of Aβ back into the brain during the passage of the subsequent pulse wave. In this study, we show first that apolipoprotein E co-localizes with Aβ in basement membrane drainage pathways in the walls of arteries. Secondly, we show by Atomic Force Microscopy that attachment of ApoE4/Aβ complexes to basement membrane laminin is significantly weaker than ApoE3/Aβ complexes. These results suggest that perivascular elimination of ApoE4/Aβ complexes would be less efficient than with other isoforms of apolipoprotein E, thus endowing a higher risk for Alzheimer's disease. Therapeutic correction for ApoE4/Aβ/laminin interactions may increase the efficiency of elimination of Aβ in the prevention of Alzheimer's disease. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.