This report describes Alzheimer disease 2 (AD2), which is a subtype of Alzheimer disease. The human gene implicated in this disease is apolipoprotein E (APOE); the E4 (or ε4) variant of APOE is associated with significantly increased risk of late-onset Alzheimer disease. Defects in APOE protein can result in increased plasma cholesterol and triglycerides and the APOE gene is implicated in several other diseases (see MIM:107741). There is no fly gene identified as orthologous to human APOE.
UAS constructs of Hsap\APOE corresponding to the E2, E3 and E4 variants have been introduced into flies. Overexpression of either E3 or E4 in neural tissues results in neuroanatomy defects, reduced longevity, and memory defects. The E4 variant exhibits defective response to oxidative stress, resulting in increased neurotoxicity when exposed to paraquat; in the same assay the E3 variant appears to have a neuroprotective effect.
Variant(s) implicated in human disease tested (as transgenic human gene): the E4 (R112, R158) variant has been introduced into flies. The E3 (C112, R158) and E2 (C112, C158) variants, which are not associated with increased risk of AD, have also been characterized in flies. These are the most common variants in human populations; E3 is the most frequent variant.
The E2, E3 and E4 variants of Hsap\APOE were assessed for ability to rescue phenotypes observed for glial knockout of the fly gene GLaz, which is one of two fly apolipoprotein genes orthologous to human APOD. Heterologous rescue (functional complementation) is observed for glial expression of human E2 or E3, but not E4.
[updated Jan. 2018 by FlyBase; FBrf0222196]
Alzheimer disease (AD) is the most common form of progressive dementia in the elderly. [from MIM:104300; 2016.01.08]
Memory loss is the most common sign of Alzheimer disease. As the disorder progresses, some people with AD experience personality and behavioral changes; other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. Total care is usually required during the advanced stages of the disease. Affected individuals usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Death usually results from pneumonia, malnutrition, or general body wasting. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
Alzheimer disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear before age 65, while the late-onset form appears after age 65. The early-onset form is much less common than the late-onset form, accounting for less than 5 percent of all cases of Alzheimer disease. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
[ALZHEIMER DISEASE 2; AD2](https://omim.org/entry/104310)
[APOLIPOPROTEIN E; APOE](https://omim.org/entry/107741)
See general description of Alzheimer disease.
A specific variant of apolipoprotein E (APOE), the E4 (or ε4) allele, is associated with significantly increased risk of late-onset Alzheimer disease (AD); worldwide, the frequency of this allele is approximately 14%. Although there is some variation between different racial and ethnic groups, the frequency of AD and mean age at clinical onset are approximately 91% and 68 years of age in E4 homozygotes; approximately 47% and 76 years of age in E4 heterozygotes; and approximately 20% and 84 years of age in E4 non-carriers (Liu, et al., 2013; pubmed:23296339).
The protein apolipoprotein E (APOE) is a major apoprotein of the chylomicron; it binds to a specific receptor on liver cells and peripheral cells. Defects in APOE protein can result in increased plasma cholesterol and triglycerides, the consequence of impaired clearance of chylomicron and VLDL (very low density lipoprotein) remnants. [from MIM:107741; 2016.11.18]
There is no Drosophila gene identified as an ortholog of APOE.
