Leaky memories: Impact of <i>APOE4</i> on blood–brain barrier and dementia

Li, Wenlu; Lo, Eng H.

doi:10.1177/0271678x20938146

Cited by 8 publications

(7 citation statements)

References 10 publications

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“…Finally, given emerging evidence of hemodynamic dysregulation and BBB leakage in asymptomatic APOEe4 carriers at midlife, the association of the two factors warrants further investigation in future studies. 56,68 In conclusion, we found evidence of higher baseline CBF in APOEe4 carriers and lower CVRi consistent with the vascular compensation hypothesis. Contrary to our hypothesis, longitudinal changes were similar between the groups, suggesting that at this point in the lifecourse, hemodynamic impairment is not accelerated.…”

Section: Discussionsupporting

confidence: 87%

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Evidence of cerebral hemodynamic dysregulation in middle-aged APOE ε4 carriers: The PREVENT-Dementia study

Dounavi

Low

McKiernan

et al. 2021

J Cereb Blood Flow Metab

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Accumulating evidence suggests vascular dysregulation in preclinical Alzheimer’s disease. In this study, cerebral hemodynamics and their coupling with cognition in middle-aged apolipoprotein ε4 carriers (APOEε4+) were investigated. Longitudinal 3 T T1-weighted and arterial spin labelling MRI data from 158 participants (40–59 years old) in the PREVENT-Dementia study were analysed (125 two-year follow-up). Cognition was evaluated using the COGNITO battery. Cerebral blood flow (CBF) and cerebrovascular resistance index (CVRi) were quantified for the flow territories of the anterior, middle and posterior cerebral arteries. CBF was corrected for underlying atrophy and individual hematocrit. Hemodynamic measures were the dependent variables in linear regression models, with age, sex, years of education and APOEε4 carriership as predictors. Further analyses were conducted with cognitive outcomes as dependent variables, using the same model as before with additional APOEε4 × hemodynamics interactions. At baseline, APOEε4+ showed increased CBF and decreased CVRi compared to non-carriers in the anterior and middle cerebral arteries, suggestive of potential vasodilation. Hemodynamic changes were similar between groups. Interaction analysis revealed positive associations between CBF changes and performance changes in delayed recall (for APOEε4 non-carriers) and verbal fluency (for APOEε4 carriers) cognitive tests. These observations are consistent with neurovascular dysregulation in middle-aged APOEε4+.

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Section: Discussionsupporting

confidence: 87%

“…Finally, given emerging evidence of hemodynamic dysregulation and BBB leakage in asymptomatic APOEε4 carriers at midlife, the association of the two factors warrants further investigation in future studies. 56 , 68 …”

Section: Discussionmentioning

confidence: 99%

Evidence of cerebral hemodynamic dysregulation in middle-aged APOE ε4 carriers: The PREVENT-Dementia study

Dounavi

Low

McKiernan

et al. 2021

J Cereb Blood Flow Metab

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“…The critical neurovascular mechanisms by which functional and phenotypic alterations of the cerebral microcirculation [ 231 , 232 , 233 ] may promote the pathogenesis of VCI in older adults include cerebral microvascular rarefaction [ 234 ], impairment of neurovascular coupling responses (also known as functional hyperemia, which is responsible for moment-to-moment adjustment of cerebral blood flow to increased oxygen and nutrient demand of activated neurons [ 235 , 236 , 237 , 238 , 239 , 240 ]), and disruption of the blood–brain barrier [ 214 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 ]. VDR is known to be expressed on each cell type within the neurovascular unit, including endothelial cells, smooth muscle cells, pericytes [ 249 ], astrocytes, and neurons [ 250 ].…”

Section: Vitamin D Deficiency Cerebrovascular Diseases Stroke and Vas...mentioning

confidence: 99%

Role of Vitamin D Deficiency in the Pathogenesis of Cardiovascular and Cerebrovascular Diseases

et al. 2023

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Deficiency in vitamin D (VitD), a lipid-soluble vitamin and steroid hormone, affects approximately 24% to 40% of the population of the Western world. In addition to its well-documented effects on the musculoskeletal system, VitD also contributes importantly to the promotion and preservation of cardiovascular health via modulating the immune and inflammatory functions and regulating cell proliferation and migration, endothelial function, renin expression, and extracellular matrix homeostasis. This brief overview focuses on the cardiovascular and cerebrovascular effects of VitD and the cellular, molecular, and functional changes that occur in the circulatory system in VitD deficiency (VDD). It explores the links among VDD and adverse vascular remodeling, endothelial dysfunction, vascular inflammation, and increased risk for cardiovascular and cerebrovascular diseases. Improved understanding of the complex role of VDD in the pathogenesis of atherosclerotic cardiovascular diseases, stroke, and vascular cognitive impairment is crucial for all cardiologists, dietitians, and geriatricians, as VDD presents an easy target for intervention.

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“…As the "neurovascular unit", the BBB includes pericytes, astrocytes, smooth muscle cells, microglia, and neurons. 16,39,40 The capillary-astrocyte complex of the neurovascular unit has been proposed as the site of CSF and brain ISF production and exchange. ISF fills the extracellular space between neurons and glia in the brain parenchyma.…”

Section: Csf Formationmentioning

confidence: 99%

A new perspective on cerebrospinal fluid dynamics after subarachnoid hemorrhage: From normal physiology to pathophysiological changes

Fang

Huang

Wang

et al. 2021

J Cereb Blood Flow Metab

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Knowledge about the dynamic metabolism and function of cerebrospinal fluid (CSF) physiology has rapidly progressed in recent decades. It has traditionally been suggested that CSF is produced by the choroid plexus and drains to the arachnoid villi. However, recent findings have revealed that the brain parenchyma produces a large portion of CSF and drains through the perivascular glymphatic system and meningeal lymphatic vessels into the blood. The primary function of CSF is not limited to maintaining physiological CNS homeostasis but also participates in clearing waste products resulting from neurodegenerative diseases and acute brain injury. Aneurysmal subarachnoid hemorrhage (SAH), a disastrous subtype of acute brain injury, is associated with high mortality and morbidity. Post-SAH complications contribute to the poor outcomes associated with SAH. Recently, abnormal CSF flow was suggested to play an essential role in the post-SAH pathophysiological changes, such as increased intracerebral pressure, brain edema formation, hydrocephalus, and delayed blood clearance. An in-depth understanding of CSF dynamics in post-SAH events would shed light on potential development of SAH treatment options. This review summarizes and updates the latest physiological characteristics of CSF dynamics and discusses potential pathophysiological changes and therapeutic targets after SAH.

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Leaky memories: Impact of APOE4 on blood–brain barrier and dementia

Cited by 8 publications

References 10 publications

Evidence of cerebral hemodynamic dysregulation in middle-aged APOE ε4 carriers: The PREVENT-Dementia study

Evidence of cerebral hemodynamic dysregulation in middle-aged APOE ε4 carriers: The PREVENT-Dementia study

Role of Vitamin D Deficiency in the Pathogenesis of Cardiovascular and Cerebrovascular Diseases

A new perspective on cerebrospinal fluid dynamics after subarachnoid hemorrhage: From normal physiology to pathophysiological changes

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