Alterations of Alzheimer's Disease in the Cholesterol‐fed Rabbit, Including Vascular Inflammation: Preliminary Observations

Sparks, David L.; Kuo, Yu Min; Roher, Alex E.; Martin, Tim; Lukas, Ronald J.

doi:10.1111/j.1749-6632.2000.tb06384.x

Cited by 172 publications

(124 citation statements)

References 26 publications

(58 reference statements)

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“…Cholesterol-rich diets suppress clearance of apo E-rich remnant lipoproteins by high-affinity pathways and via heightened inflammatory processes. 49 ) with negative numbers being indicative of an inverse relationship. Probability of a significant correlation is indicated for P values better than 0.05…”

Section: Discussionmentioning

confidence: 99%

Plasma lipoprotein β-amyloid in subjects with Alzheimer's disease or mild cognitive impairment

et al. 2008

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Background: Plasma amyloid b-peptide (Ab) can compromise the blood-brain barrier, contributing to cerebrovascular alterations and amyloid angiopathy in Alzheimer's disease (AD). The objectives of this study were to investigate the distribution of lipoprotein-bound plasma-Ab isoforms.Methods: This involved a case-control study of subjects with AD or amnestic mild cognitive impairment (MCI) versus controls. Lipoprotein Ab distribution was determined in fasted plasma. For assessment of chylomicron homeostasis in the postabsorptive state, subjects were bled 4 h after a low-fat meal. The main outcome measures were plasma lipoprotein Ab isoform distribution and lipid homeostasis. Results: We found the majority of plasma Ab to be associated with triglyceride-rich lipoproteins (TRLs) encompassing chylomicrons, VLDL and IDL. For all lipoprotein groups, Ab 1 -40 was the predominant isoform, accounting for approximately 50% of the total. Thereafter, equivalent amounts of the isoforms 1 -42, 2-40, 1 -38, 1-37 and 1 -39 were found. Ab 1 -37 , Ab 1 -38 and Ab 2 -40 isoforms were significantly enriched within the TRL fraction of AD/MCI subjects and similar trends were observed for isoforms Ab 1 -39 , Ab 1 -40 and Ab 1 -42 . Lipoprotein-Ab was inversely associated with plasma total-and LDL cholesterol. AD/MCI subjects were not dyslipidaemic, however, there was evidence of accumulation of chylomicrons in the postabsorptive state. Conclusions: Our data show that Ab was found to be associated with plasma lipoproteins, especially those enriched with triglyceride. We find that Ab may be increased in normolipidaemic AD subjects, commensurate with possible disturbances in postprandial lipoprotein homeostasis.

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Section: Discussionmentioning

confidence: 99%

Plasma lipoprotein β-amyloid in subjects with Alzheimer's disease or mild cognitive impairment

et al. 2008

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“…In addition to cholesterol, which decreases the membrane fluidity [15,35,72,109] there are some molecules that fluidize the membrane. Prominent among them is alcohol (e.g.…”

Section: Membrane Fluiditymentioning

confidence: 99%

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

Yehuda¹,

Rabinovitz²,

Carasso³

et al. 2002

Neurobiology of Aging

348

200

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In addition to a gradual loss of neurons in various brain regions, major biochemical changes in the brain affect the neuronal membrane that is the "site of action" for many essential functions including long-term potentiation (LTP), learning and memory, sleep, pain threshold, and thermoregulation. Normal physiological functioning includes the transmission of axonal information, regulation of membrane-bound enzymes, control of ionic channels and various receptors. All are highly dependent on membrane fluidity, where rigidity is increased during aging. The significantly higher level of cholesterol in aging neuronal membrane, the slow rate of cholesterol turnover, and the decreased level of total polyunsaturated fatty acids (PUFA) may result from poor passage rate via the blood-brain barrier, or from a decreased rate of incorporation into the membrane, or a decrease in the activities of delta-6 and delta-9 desaturase enzymes. The added oxidative stress, which leads to an increase of free radicals leading to a decrease in membrane fluidity, may respond to a restricted diet, and thereby overcome the damaging effects of the free radicals. A central focus of this review is that a specific ratio of n-3/n-6 PUFA can restore many of these age-related effects.

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“…Employing this approach, we demonstrated that the α5 integrin subunit is expressed specifically by angiogenic endothelial cells within the hypoxic CNS. Two other studies have described re-expression of the MECA-32 antigen on endothelial cells in the adult brain during neuroinflammatory conditions (Engelhardt et al, 1994;Sparks et al, 2000). In one of these, injection of Corynebacterium parvum induced endothelial expression of ICAM-1 and VCAM-1 on all vessels throughout the CNS, but MECA-32 expression on endothelial cells only at the center of the inflammatory infiltrate (Engelhardt et al, 1994).…”

Section: Temporal Expression Pattern Of Fibronectin α5 Integrin and mentioning

confidence: 99%

Increased expression of fibronectin and the α5β1 integrin in angiogenic cerebral blood vessels of mice subject to hypobaric hypoxia

Milner

Hung

Erokwu

et al. 2008

Molecular and Cellular Neuroscience

120

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The extracellular matrix (ECM) is an important regulator of angiogenesis and vascular remodeling. We showed previously that angiogenic capillaries in the developing CNS express high levels of fibronectin and its receptor α5β1 integrin, and that this expression is developmentally downregulated. As cerebral hypoxia leads to an angiogenic response, we sought to determine whether angiogenic vessels in the adult CNS re-express fibronectin and the α5β1 integrin. Ten-week old mice were subject to hypobaric hypoxia for 0, 4, 7 and 14 days, and fibronectin/integrin expression examined. Fibronectin and the α5 integrin subunit were strongly upregulated on capillaries in the hypoxic CNS, with the effect maximal at the earliest time point examined (4 days). Immunofluorescent studies demonstrated that the α5 integrin was expressed by angiogenic endothelial cells. In light of the defined angiogenic role for fibronectin in other systems, this work suggests that induction of fibronectin-α5β1 integrin expression may be an important molecular switch driving angiogenesis in the hypoxic CNS.

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Alterations of Alzheimer's Disease in the Cholesterol‐fed Rabbit, Including Vascular Inflammation: Preliminary Observations

Cited by 172 publications

References 26 publications

Plasma lipoprotein β-amyloid in subjects with Alzheimer's disease or mild cognitive impairment

Plasma lipoprotein β-amyloid in subjects with Alzheimer's disease or mild cognitive impairment

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

Increased expression of fibronectin and the α5β1 integrin in angiogenic cerebral blood vessels of mice subject to hypobaric hypoxia

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