Initially identified in an analysis of two genome-wide association studies (FBrf0223922), the human gene CD2AP is proposed as a candidate susceptibility locus for Alzheimer disease. CD2AP encodes a scaffolding molecule that acts as an adapter protein between membrane proteins and the actin cytoskeleton. There is a single fly ortholog, cindr, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated. Dmel\cindr is orthologous to two additional human genes, SH3KBP1 and SH3D21. CD2AP has also been implicated in susceptibility to the renal disease focal segmental glomerulosclerosis-3 (MIM:607832; see FBhh0000618).
Multiple UAS constructs of the human Hsap\CD2AP gene have been introduced into flies, but have not been characterized in the context of this disease.
The fly ortholog cindr was tested for genetic interaction with a transgenically introduced mutational variant of the human tau gene (Hsap\MAPT); RNAi-mediated reduction in the expression of cindr was observed to enhance the phenotype associated with tau toxicity. Physical and genetic interactions of Dmel\cindr have been characterized; see below and in the gene report for cindr.
[updated Oct. 2017 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]
Locus identified as showing significant association with susceptibility to Alzheimer disease in an analysis of two genome-wide association studies (GWAS).
CD2AP is associated with Alzheimer disease in multiple GWAS studies (see GWAS Catalog, below in 'External links').
A large genome-wide association meta-analysis of clinically diagnosed late-onset Alzheimer's disease (94,437 individuals) supports previous studies implicating CD2AP as a susceptibility locus for AD (Kunkle et al., 2019; pubmed:30820047).
CD2AP encodes an adapter protein between membrane proteins and the actin cytoskeleton and appears to have a role in the regulation of actin remodeling and membrane trafficking that occurs during receptor endocytosis and cytokinesis. [from Gene Cards, CD2AP; 2016.06.02]
Many to one: 3 human to 1 Drosophila; the fly gene cindr is orthologous to SH3KBP1, CD2AP, and SH3D21 in human.
Moderate-scoring ortholog of human genes SH3KBP1, CD2AP, and SH3D21 (1 Drosophila to 3 human). Dmel\cindr shares 21-26% identity and 33-36% similarity with the human genes.
