Background. Blood-brain barrier (BBB) dysfunction may have a significant role in the pathogenesis of Alzheimer's disease (AD). Modifiable factors associated with BBB function may have therapeutic implication. This study tested the hypothesis that dyslipidemia is associated with BBB impairment in mild-to-moderate AD. Methods. Thirty-six subjects with AD were followed for 1 year. Fasting CSF and plasma were collected with clinical assessments at baseline and 12 months. BBB impairment was defined as CSF albumin index ≥9. Independent t-tests and linear regression assessed the relationship between plasma lipoproteins and BBB integrity. Results. Dyslipidemia was prevalent in 47% of the population, and in 75% of those with BBB impairment. Subjects with BBB impairment had significantly higher mean plasma triglyceride and lower HDL cholesterol (TG, ; HDL, ). Plasma triglycerides explained 22% of the variance in BBB integrity and remained significant after controlling for age, gender, ApoE-4 genotype, blood pressure, and statin use. Conclusion. Dyslipidemia is more prevalent in AD subjects with BBB impairment. Plasma triglyceride and HDL cholesterol may have a role in maintaining BBB integrity in mild-to-moderate Alzheimer's disease. 1. Introduction The CSF albumin index is an established measure of blood-brain barrier (BBB) integrity in living patients [1]. This index has detected a higher prevalence of BBB impairment in late onset dementia, including both Alzheimer’s disease (AD) and vascular dementia compared to cognitively intact elders [2]. BBB impairment is associated with more rapid rate of decline in AD over 1 year [3]. Capillary endothelia dysfunction and the approximate tight junctions between these cells may be important to AD pathogenesis, including effects on maintaining cerebral perfusion and the clearance of toxic forms of beta-amyloid protein [4, 5]. The notion that the BBB is central to the pathogenesis of AD is controversial, but the enormity of the cerebrovascular tree and the similarity in risk factors between vascular and Alzheimer’s disease makes the BBB and neurovascular unit difficult to disregard [6, 7]. If BBB function plays a role in the pathogenesis of AD, then modifiable factors associated with it may have therapeutic potential. A clinical trial of B vitamin supplementation has suggested that the BBB may be a modifiable entity in subjects with hyperhomocysteinemia and mild cognitive impairment [8]. Lipids are plausible candidates for modifying BBB function because of their relationship with vascular disease and ability to affect AD
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