Term
| What genotype is a common factor in both Alheimer's and Coronary Heart Disease? |
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Definition
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Term
| Where is ApoE synthesized and what lipoproteins does it associate with? |
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Definition
| Liver (most of plasma pool), brain (most of CNS pool), skin, macrophages, and steriodogenic organs. It associates with chylomicrons, VLDL, and HDL (50% of total associated with HDL). |
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Term
| What lipoprotein receptors recognize ApoE? |
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Definition
| 1) LDL receptor, 2) VLDL receptor (aka remnant receptor aka ApeE receptor), and 3) LDL-related protein (LRP aka A2-macroglobulin receptor) |
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Term
| How are remnants taken up in neurons? |
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Definition
| LP's transfer to LPR on cell membrane or bind to HSPG/LPR complex and are internalized. |
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Term
| How many isoforms of ApoE are there? |
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Definition
| Three: E2 (cys112/cys158), E3 (cys112/arg158), and E4 (arg112/arg158). They've got different helix r's. E3 is "normal" based on frequency in population. |
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Term
| What is wrong with ApoE2? |
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Definition
| It has defective receptor binding (<2% as effective as ApoE3 and comparable to ApoB receptor binding). |
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Term
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Definition
| Type 3 Hyperlipoproteinemia (HLP) is a genetic disorder (most common in people who are homozygous for ApoE2). It manifests as high plasma Chol and high TG's as well as low LDL. In Type 3 HLP, there is an abundance of VLDL and chylomicron remnants in the blood stream (known collectively as B-VLDL, which is rich in ApoE). More frequent and earlier-occurring in men. |
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Term
| What is Alzheimer's Disease? |
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Definition
| Familial AD is late-onset (>90%) or early-onset. ApoE variants are associated with longevity: E2 higher survival, E4 lower survival. It is unclear why this is so but the major hypotheses are based on 1) effects on AB metabolism, 2) direct effect on neurons or glial cells, and 3) effects related to atherosclerosis and the BBB. |
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Term
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Definition
| APP = amyloid precursor protein. It can be cut by either A-secretase or B-secretase (beta gives the amyloidogenic AB form following cleavage). The complex favoring the non-amyloidogenic product has been seen in mice with high cholesterol (e.g. ApoE deficient binding?). |
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Term
| How might ApoE variants be distinguished? |
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Definition
| Electrophoresis (Arg is charged) |
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Term
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Definition
| ApoC1 inhibits CETP. ApoC2 activates lipoprotein lipase. ApoC3 inhibits lipase activity and prevents binding of VLDL to cell surface glycans. |
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