Albumin and immunoglobulin in plasma and cerebrospinal fluid, and blood-cerebrospinal fluid barrier function in patients with dementia of Alzheimer type and multi-infarct dementia

ArticleinJournal of the Neurological Sciences 60(3):465-472 · August 1983with10 Reads
DOI: 10.1016/0022-510X(83)90157-0
Abstract
Plasma and cerebrospinal fluid (CSF) from 20 patients with Alzheimer's dementia or senile dementia of Alzheimer type (AD/SDAT), 23 with multi-infarct dementia (MID) and 16 controls were assayed for their content of immunoglobulins (Ig) and albumin (Alb). The concentrations of IgG and Alb were used to analyze the blood-CSF barrier function in the respective group.MID patients had significantly (P < 0.001) elevated plasma IgG levels compared to controls and AD/SDAT patients. CSF concentration of Alb was significantly higher in MID (P < 0.01) and AD/SDAT (P < 0.05) patients compared to the controls. Concentration of CSF IgG was significantly (P < 0.05) lower in AD/SDAT patients compared to the MID patients; no significant differences were found when CSF concentrations of IgG of demented patients were compared to controls. These findings may indicate a blood-CSF barrier dysfunction especially in cases with MID with significantly (P < 0.001) elevated values of transudation. Also these findings indicate a non-specific and/or specific binding of IgG in CNS tissue and/or vessel walls in both forms of dementia on the basis of low IgG ratios compared to proportionally higher Alb ratios.There were no signs of local synthesis of IgG in CNS in either group of demented patients.
    • "Levels of sPLA 2 in AD patients were found to increase in association with BBB compromise as compared to controls, suggesting its potential utility as a biomarker. Increased levels of albumin in the CSF of AD and multi-infarct dementia (a subtype of VaD) patients compared to controls have also been reported [36]. Similarly, increased CSF/serum IgG and albumin ratios (which compares albumin levels in the blood and CSF) have been shown in both ambulatory and institutionalized AD patients [37]. "
    [Show abstract] [Hide abstract] ABSTRACT: Alzheimer’s disease (AD) and diabetes mellitus (DM) are among the most pervasive and devastating disorders that afflict people throughout the world. Although typically associated with older demographics, recent epidemiologic studies have reported parallel trends in decreasing age of onset and increasing incidence of these conditions. Promising research continues to implicate the cerebrovasculature and blood-brain barrier (BBB) as playing key roles in AD pathoetiology. Similarly, complications accompanying DM, such as diabetic nephropathy/retinopathy, cardiovascular disease, and stroke, have been rooted in vascular compromise. Not surprisingly, DM is now considered a major risk factor for AD. The purpose of this review is to highlight investigations into the role of the cerebrovasculature in the development and progression of AD. We give particular attention to studies on humans and a variety of animal model systems that have demonstrated a link between BBB dysfunction and pathological changes in the brain consistent with aging and AD. Together, these studies suggest that the vascular complications associated with chronic, poorly managed DM can lead to subclinical BBB breakdown that precedes and drives the pathological changes progressing to symptomatic AD, providing a common mechanistic thread connecting these two disorders. Furthermore, this emphasizes the need to focus on the vasculature as a potential therapeutic target with the intent of limiting BBB breakdown involved in disease initiation and progression. In conclusion, AD may be more than just an associated comorbidity of DM, and instead another manifestation of the underlying vascular pathology that is common to both.
    Full-text · Article · Jul 2016
    • "The associated pathologic changes in the parenchymal small arteries and arterioles (e.g., arteriolosclerotic changes such as fibrinoid necrosis, lipohylinosis, microatheroma, and microaneurysms) extend to the endothelial barriers of the small vessels and capillaries (i.e., the BBB) resulting in permeability changes and extravasation of plasma components into the vessel walls and brain parenchyma [19]. Postmortem analyses of AD brain tissue have demonstrated changes to the microvasculature through the presence of extravasated serum proteins, such as albumin and immunoglobulin [20][21][22][23], as well as white matter lesions and the widespread deposition of cerebral amyloid angiopathy, with associated microbleeds; all of which may contribute to decline in vascular integrity and function [19]. These observations, together with the findings from the nonclinical models, informed on the choice of AD subjects with neuroimaging evidence of CVD (e.g., white matter lesions and/or lacunes, typical of SVD) in the present study. "
    [Show abstract] [Hide abstract] ABSTRACT: Background The lipoprotein-associated phospholipase A2 inhibitor (Lp-PLA2), rilapladib (SB659032), is being evaluated as a potential treatment to slow the progression of Alzheimer's disease (AD). Methods One hundred twenty-four subjects with possible mild AD and with neuroimaging evidence of cerebrovascular disease were randomized to placebo or 250-mg rilapladib once daily, for 24 weeks, in addition to stable background acetylcholinesterase inhibitor and/or memantine. The study assessed the safety and tolerability of rilapladib and its effects on cognition, mechanistic, and disease-related biomarkers. Although the overall intent behind the study was to take a broad exploratory view of the data, two primary end points of interest (cerebrospinal fluid [CSF] amyloid beta peptide 1-42 [Aβ1-42] and CogState executive function/working memory [EF/WM] composite score at week 24) were prespecified in the analysis plan for inferential statistical analysis. Results Rilapladib was well tolerated with no significant safety concerns. A significant difference from placebo was observed for rilapladib on change from baseline in EF/WM (effect size, 0.45; P =.026). There was no significant difference between groups on the change from baseline in CSF Aβ1-42 (P =.133). Preliminary evidence of effects was detected on other mechanistic (albumin quotient) and disease-related biomarkers (tau/P-tau and neurofilament light chain). Conclusion These data provide initial evidence supporting Lp-PLA2 inhibition as a novel treatment for dementia. Clinical Trial Registration Clinicaltrials.gov identifier: NCT01428453.
    Full-text · Article · Jun 2015
    • "oxysterols possibly reflect neuronal death with release of cell membrane cholesterol . Other factors that will affect cholesterol equilibrium include the disturbances and degeneration of the BBB which occur as part of the neuropathology in AD brains ( Claudio 1996 ; Kalaria 1996 , 2002 ) ; however , this is also seen in many non - AD aged brains ( Alafuzoff et al . 1983 ; Hampel et al . 1995 , 1997 ) . Polymorphisms in the CYP46 gene have been associated with the pathophysiology and the incidence of AD ( Kolsch et al . 2002 ; Papassotiropoulos et al . 2003 ) , and some studies have shown evidence that CYP46 and APOE polymorphisms synergistically increase the risk for AD development , and influence the "
    [Show abstract] [Hide abstract] ABSTRACT: Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting millions of people worldwide. Apart from age, the major risk factor identified so far for the sporadic form of AD is possession of the epsilon4 allele of apolipoprotein E (APOE), which is also a risk factor for coronary artery disease (CAD). Other apolipoproteins known to play an important role in CAD such as apolipoprotein B are now gaining attention for their role in AD as well. AD and CAD share other risk factors, such as altered cholesterol levels, particularly high levels of low density lipoproteins together with low levels of high density lipoproteins. Statins--drugs that have been used to lower cholesterol levels in CAD, have been shown to protect against AD, although the protective mechanism(s) involved are still under debate. Enzymatic production of the beta amyloid peptide, the peptide thought to play a major role in AD pathogenesis, is affected by membrane cholesterol levels. In addition, polymorphisms in several proteins and enzymes involved in cholesterol and lipoprotein transport and metabolism have been linked to risk of AD. Taken together, these findings provide strong evidence that changes in cholesterol metabolism are intimately involved in AD pathogenic processes. This paper reviews cholesterol metabolism and transport, as well as those aspects of cholesterol metabolism that have been linked with AD.
    Full-text · Article · Dec 2009
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