Apolipoprotein E &amp;isin;4 allele distributions in late-onset Alzheimer's disease and in other amyloid-forming diseases

Saunders, Ann M.; Roses, Allen D.; Pericak‐Vance, M. A.; Dole, Kenneth C.; Strittmatter, Warren J.; Schmechel, Donald E.; Szymanski, Mari H.; McCown, N.; Manwaring, M.; Schmader, Ken; Breitner, John C.S.; Goldgaber, Dmitry; Benson, Merrill D.; Goldfarb, Lev G.; Brown, W. Ted

doi:10.1016/0140-6736(93)91709-u

Cited by 472 publications

(201 citation statements)

References 5 publications

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“…9 The major genetic risk factor for late-onset (non-familial) AD is carriage of the apolipoprotein E e4 allele (APOE e4). 10 The presence of APOE e4 is associated with a greater cholinergic deficit 11 and rate of cognitive decline 12 than in non-carriers of APOE e4, suggesting a likelihood of poorer clinical response to ChEI treatment. Gender may interact with APOE genotype in cognitive decline and, therefore, may also be a predictor of response.…”

Section: Introductionmentioning

confidence: 99%

Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease

2010

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Section: Introductionmentioning

confidence: 99%

Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease

2010

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“…Although the function, if any, of lipoproteins in the pathogenesis of prion disease is unknown, the role of apolipoprotein E (apoE) in modulating the onset of Alzheimer's disease is well documented (41). Attempts to correlate the apoE isotype with sCJD were unsuccessful (42,43), and apoE-deficient mice exhibited incubation times for RML prions that were indistinguishable from those in WT mice (44).…”

Section: Prions In Bloodmentioning

confidence: 99%

Human prions and plasma lipoproteins

Safar

Wille

Geschwind

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Prions are composed solely of an alternatively folded isoform of the prion protein (PrP), designated PrP Sc . The polyoxometalate phosphotungstic acid has been used to separate PrP Sc from its precursor PrP C by selective precipitation; notably, native PrP Sc has not been solubilized by using nondenaturing detergents. Because of the similarities between PrP Sc and lipoproteins with respect to hydrophobicity and formation of phosphotungstic acid complexes, we asked whether these molecules are bound to each other in blood. Here we report that prions from the brains of patients with sporadic Creutzfeldt-Jakob disease (CJD) bind to very low-density (VLDL) and low-density (LDL) lipoproteins but not to high-density lipoproteins (HDL) or other plasma components, as demonstrated both by affinity assay and electron microscopy. Immunoassays demonstrated that apolipoprotein B (apoB), which is the major protein component of VLDL and LDL, bound PrP Sc through a highly cooperative process. Approximately 50% of the PrP Sc bound to LDL particles was released after exposure to 4 M guanidine hydrochloride at 80°C for 20 min. The apparent binding constants of native human (Hu) PrP Sc or denatured recombinant HuPrP(90 -231) for apoB and LDL ranged from 28 to 212 pM. Whether detection of PrP Sc in VLDL and LDL particles can be adapted into an antemortem diagnostic test for prions in the blood of humans, livestock, and free-ranging cervids remains to be determined. prion protein ͉ apolipoprotein B ͉ blood ͉ Creutzfeldt-Jakob disease P rions are composed solely of an alternatively folded isoform of the prion protein, designated PrP Sc . Despite numerous efforts to solubilize native PrP Sc , no procedure has been developed except for incorporation of the protein into liposomes (1, 2). The hydrophobic properties of PrP Sc not only have impeded biological investigations but also have prevented structural studies at atomic resolution.During the development of an immunoassay for PrP Sc that does not depend upon limited proteolysis to hydrolyze the precursor protein designated PrP C , we found that the Na salt of phosphotungstic acid (PTA) selectively complexes with PrP Sc (3). PTA is a water-soluble salt featuring the nearly spherical trianion [PW 12 O 14 ] 3Ϫ that belongs to a broad class of polynuclear transition metal-oxo complexes known as polyoxometalates (POMs; see ref. 4). Recently, two of us (J.G.S. and S.B.P.) investigated the mechanism of selective complex formation between Keggin-type POMs and PrP Sc using a series of POM analogues (5). The ability of POMs to complex with PrP Sc as well as lipoproteins (6) raised the possibility that these two hydrophobic proteins might copurify.We began by examining the distribution of human (Hu) PrP Sc in human plasma fractions spiked with sporadic CreutzfeldtJakob disease (sCJD) prions from human brain. CJD prions were found with very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) but not with high-density lipoproteins (HDL) or any other plasma component. In addition to b...

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“…9 Individuals carrying the APOE ⑀4 allele have higher plasma and neuronal levels of cholesterol than individuals with ⑀2 or ⑀3 and the ⑀4 allele is strongly linked with Alzheimer's disease in both familial and sporadic forms. [9][10][11] ApoE also has an isoform-specific effect on neuronal growth with E3 stimulating and E4 impairing neuronal elongation and neurite outgrowth in dorsal root ganglia. 12 The abnormalities of the neuronal dendrites and their synaptic spines reported in neurological cretinism bear a striking resemblance to those reported in Alzheimer's disease especially among APOE ⑀4 carriers.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E is a genetic risk factor for fetal iodine deficiency disorder in China

et al. 2000

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Fetal iodine deficiency disorder (FIDD) is the principal form of endemic cretinism, and the most common cause of preventable mental deficiency in the world. However not everyone at risk develops FIDD and familial aggregation is common. This suggests that genetic factors may also be involved. The Apolipoprotein E (APOE) gene encodes for a lipoprotein that possesses a thyroid hormone binding domain, and APOE genotype may affect the efficiency with which thyroid hormone influences neuronal cell growth during the first and second trimesters of fetal development. We have compared ApoE genotypes in 91 FIDD cases with 154 local control subjects, recruited from three iodine deficiency areas in central China. We have also genotyped 42 FIDD family cases and 158 normal individuals from the families of local controls, and 375 population controls from Shanghai. APOE ⑀4 genotypes were significantly enriched in FIDD probands from each of the three iodine deficiency areas; the ⑀4 allele frequency was 16% vs 6% in controls. The same effect was also observed when we compared FIDD family cases with controls and control families. Our data suggest that in iodine-deficient areas, the APOE ⑀4 allele is a genetic risk factor for FIDD. The phenomenon may affect population selection and contribute to the low frequency of the ⑀4 allele in Chinese compared to Caucasian populations. Molecular Psychiatry (2000) 5, 363-368.

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Apolipoprotein E ∈4 allele distributions in late-onset Alzheimer's disease and in other amyloid-forming diseases

Cited by 472 publications

References 5 publications

Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease

Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease

Human prions and plasma lipoproteins

Apolipoprotein E is a genetic risk factor for fetal iodine deficiency disorder in China

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