APOE and cholesterol homeostasis in Alzheimer's disease

Leduc, Valérie; Jasmin-Bélanger, Stéphanie; Poirier, Judes

doi:10.1016/j.molmed.2010.07.008

Cited by 151 publications

(131 citation statements)

References 97 publications

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“…Our results confirmed the previously described association of E4 allele and AD, (Farrer et al 1997) supporting the ApoE gene variant as a risk factor for the development of AD (Leduc et al 2010). ApoE4 allele might play an important role in the pathophysiology of AD (Leduc et al 2010;Perl 2010).…”

Section: Discussionsupporting

confidence: 92%

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Alzheimer’s disease and type 2 diabetes: the association study of polymorphisms in tumor necrosis factor-alpha and apolipoprotein E genes

et al. 2012

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Section: Discussionsupporting

confidence: 92%

“…ApoE4 allele might play an important role in the pathophysiology of AD (Leduc et al 2010;Perl 2010). The E4 carriers exhibit reduced clearance with 9 consequently higher deposition of toxic Aβ, enhanced formation of neurofibrillary tangles, and insufficient neuronal damage repair, compared to E2 and E3 carriers (Perl 2010).…”

Section: Discussionmentioning

confidence: 99%

Alzheimer’s disease and type 2 diabetes: the association study of polymorphisms in tumor necrosis factor-alpha and apolipoprotein E genes

et al. 2012

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“…Neurofibrillary degeneration has been considered absent in aging great apes (Gearing et al 1994(Gearing et al , 1996(Gearing et al , 1997. However, we now have one case of classic Alzheimer tauopathy and neurofibrillary degeneration in a 41-year-old female who was euthanized after a stroke ; this individual had notable obesity and hypercholesterolemia, which are risk factors in human AD and, which in AD-transgenic mice, accelerate neurodegeneration (Cole et al 2010;Leduc et al 2010). Numerous tau-immunoreactive paired helical filaments were found in neocortex and subcortical regions.…”

Section: Primate Neurobiologymentioning

confidence: 94%

Primate aging in the mammalian scheme: the puzzle of extreme variation in brain aging

Finch

Austad²

2012

AGE

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At later ages, humans have high risk of developing Alzheimer disease (AD) which may afflict up to 50% by 90 years. While prosimians and monkeys show more substantial changes, the great apes brains examined show mild neurodegenerative changes. Compared with rodents, primates develop and reproduce slowly and are long lived. The New World primates contain some of the shortest as well as some of the longest-lived monkey species, while the prosimians develop the most rapidly and are the shortest lived. Great apes have the largest brains, slowest development, and longest lives among the primates. All primates share some level of slowly progressive, age-related neurodegenerative changes. However, no species besides humans has yet shown regular drastic neuron loss or cognitive decline approaching clinical grade AD. Several primates accumulate extensive deposits of diffuse amyloid-beta protein (Aβ) but only a prosimian-the gray mouse lemur-regularly develops a tauopathy approaching the neurofibrillary tangles of AD. Compared with monkeys, nonhuman great apes display even milder brain-aging changes, a deeply puzzling observation. The genetic basis for these major species differences in brain aging remains obscure but does not involve the Aβ coding sequence which is identical in nonhuman primates and humans. While chimpanzees merit more study, we note the value of smaller, shorterlived species such as marmosets and small lemurs for aging studies. A continuing concern for all aging studies employing primates is that relative to laboratory rodents, primate husbandry is in a relatively primitive state, and better husbandry to control infections and obesity is needed for brain aging research.

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“…Conversely, ApoE2 has been proposed to be mildly protective for AD, although this remains a weak association without a clear mechanism (Maezawa et al 2004). ApoE4 is thought to contribute to AD mainly by altering how neurons Leduc et al 2010). The mechanism for this is complex and depends on interactions between ApoE, ApoE cell surface receptors, cholesterol, APP and Aβ, within neurons and in the surrounding astrocytes and extracellular space.…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Apolipoprotein E Isoforms and AMD

Toops

Tan

Lakkaraju

2015

Advances in Experimental Medicine and Biology

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The cholesterol transporting protein apolipoprotein E (ApoE) occurs in three allelic variants in humans unlike in other species. The resulting protein isoforms E2, E3 and E4 exhibit differences in lipid binding, integrating into lipoprotein particles and affinity for lipoprotein receptors. ApoE isoforms confer genetic risk for several diseases of aging including atherosclerosis, Alzheimer's disease, and age-related macular degeneration (AMD). A single E4 allele increases the risk of developing Alzheimer's disease, whereas the E2 allele is protective. Intriguingly, the E4 allele is protective in AMD. Current thinking about different functions of ApoE isoforms comes largely from studies on Alzheimer's disease. These data cannot be directly extrapolated to AMD since the primary cells affected in these diseases (neurons vs. retinal pigment epithelium) are so different. Here, we propose that ApoE serves a fundamentally different purpose in regulating cholesterol homeostasis in the retinal pigment epithelium and this could explain why allelic risk factors are flipped for AMD compared to Alzheimer's disease.

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APOE and cholesterol homeostasis in Alzheimer's disease

Cited by 151 publications

References 97 publications

Alzheimer’s disease and type 2 diabetes: the association study of polymorphisms in tumor necrosis factor-alpha and apolipoprotein E genes

Alzheimer’s disease and type 2 diabetes: the association study of polymorphisms in tumor necrosis factor-alpha and apolipoprotein E genes

Primate aging in the mammalian scheme: the puzzle of extreme variation in brain aging

Apolipoprotein E Isoforms and AMD

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