Cholesterol in Alzheimer's disease

Shobab, Leila; Hsiung, Ging-Yuek Robin; Feldman, Howard

doi:10.1016/s1474-4422(05)70248-9

Cited by 298 publications

(251 citation statements)

References 145 publications

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“…Hypercholesterolemia has been suggested to be an independent risk factor for developing the memory impairments associated with Alzheimer's disease (AD) [3,5,28]. In addition, a prior study reported that LDLR-/-mice exhibited impaired spatial memory in the Morris water maze [23].…”

Section: Morris Water Mazementioning

confidence: 99%

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Increased locomotor activity in mice lacking the low-density lipoprotein receptor

Elder

Ragnauth

Dorr

et al. 2008

Behavioural Brain Research

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While the low-density lipoprotein receptor (LDLR) is best known for its role in regulating serum cholesterol, LDLR is expressed in brain, suggesting that it may play a role in CNS function as well. Here, using mice with a null mutation in LDLR (LDLR-/-), we investigated whether the absence of LDLR affects a series of behavioral functions. We also utilized the fact that plasma cholesterol levels can be regulated in LDLR-/-mice by manipulating dietary cholesterol to investigate whether elevated plasma cholesterol might independently affect behavioral performance. LDLR-/-mice showed no major deficits in general sensory or motor function. However, LDLR-/-mice exhibited increased locomotor activity in an open field test without evidence of altered anxiety in either an open field or a light/dark emergence test. By contrast, modulating dietary cholesterol produced only isolated effects. While both C57BL/6J and LDLR-/-mice fed a high cholesterol diet showed increased anxiety in a light/dark task, and LDLR-/-mice fed a high cholesterol diet exhibited longer target latencies in the probe trial of the Morris water maze, no other findings supported a general effect of cholesterol on anxiety or spatial memory.

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Section: Morris Water Mazementioning

confidence: 99%

“…Interestingly, hypercholesterolemia itself has been suggested to be an independent risk factor for brain disease. In particular, elevated serum cholesterol has been suggested to increase the risk of developing Alzheimer's disease (AD) [3,5,21,28]. Why hypercholesterolemia might promote AD is not understood.…”

Section: Introductionmentioning

confidence: 99%

Increased locomotor activity in mice lacking the low-density lipoprotein receptor

Elder

Ragnauth

Dorr

et al. 2008

Behavioural Brain Research

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“…Cholesterol is reported to influence the metabolism of APP. High cholesterol is reported to increase the production of Ab and its deposition into plaques (Shobab et al, 2005). Although not fully understood, a few molecular mechanisms have been proposed: High levels of cholesterol (i) decrease membrane fluidity.…”

Section: Alzheimer's Amyloidogenic Membrane-associated Proteinsmentioning

confidence: 99%

“…With respect to AD, cholesterol has been implicated in the pathogenesis of the disease (Koudinova et al, 2003;Lesdema and Dotti, 2006;Shobab et al, 2005). Successfully capturing the distribution and concentration of cholesterol in the different phases to mimic a biological membrane would be crucial in understanding amyloidogenic-induced neurotoxicity.…”

Section: Current and Future Challenges In The Use Of Model Membranesmentioning

confidence: 99%

“…They include cholinergic, genomic, histopathologic, inflammation mediators, oxidative stress, metabolic, and hormonal (Vestergaard et al, 2006). More recently, changes in cholesterol concentration and homeostasis have been linked to AD (Koudinova et al, 2003;Lesdema and Dotti, 2006;Shobab et al, 2005), although the biochemical mechanisms underlying its impact on the onset and progress of the pathology remain largely unknown. The use of model cell membrane systems have greatly increased our understanding of some of the biochemical processes underlining the development and progress of AD (Curtain et al, 2003;Kalvodova et al, 2005;Kojro et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Using model membranes for the study of amyloid beta:lipid interactions and neurotoxicity

Vestergaard

Hamada

Takagi

2008

Biotech & Bioengineering

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One of the major tasks in understanding the etiopathogenesis of amyloid beta-induced neurotoxicity of Alzheimer's disease (AD), is in fully capturing the large number of the biochemical processes that influence each other during the course of the disease, in vivo. Model membranes possess, as their main strength, the ability to enable the researcher to manipulate a 'biological' microvesicle under a controlled environment. This review narrowly focuses on discussing the exploitation of model membranes for improved understanding of some of the mechanisms governing AD's amyloid beta-induced neurotoxicity. Amyloid beta (Ab) is cleaved from a membranelocated amyloid precursor protein by membrane-located enzymes. The relative spatial localization of the involved biomolecules within the membrane bilayer is crucial in influencing Ab production, its aggregation on the membrane surface or insertion into the membrane, and fibril formation: all important processes in causing neurotoxicity. The lipid composition of the bilayer is similarly important. The review also attempts to highlight current and future challenges in using model membranes for studying biochemical processes.

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Vascular Factors and Markers of Inflammation in Offspring With a Parental History of Late-Onset Alzheimer Disease

Exel¹,

Eikelenboom²,

Comijs³

et al. 2009

Arch Gen Psychiatry

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Cholesterol in Alzheimer's disease

Cited by 298 publications

References 145 publications

Increased locomotor activity in mice lacking the low-density lipoprotein receptor

Increased locomotor activity in mice lacking the low-density lipoprotein receptor

Using model membranes for the study of amyloid beta:lipid interactions and neurotoxicity

Vascular Factors and Markers of Inflammation in Offspring With a Parental History of Late-Onset Alzheimer Disease

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