Newly discovered CLU gene involved in Alzheimer’s Disease

Incurable. Progressively degenerative. Terminal.

Alzheimer’s Disease (AD) is the most common form of dementia, a highly damaging brain disorder. Until recently, only one gene, APOE4, had been shown to be associated with AD, and this was way back in 1993. However, in June this year, three new genes – CLU, CR1 and PICALM were discovered through an AD genome-wide association study. A discovery that has researchers quietly optimistic about better understanding AD.

The CLU gene encodes a protein called clusterin which is associated with the clearance of cellular debris such as amyloid. Levels of clusterin tend to rise in order to protect the brain when the brain tissue becomes inflamed or injured. Mutations within CLU may remove the protective benefit of clusterin. There is a high probability this could lead to AD, which is partially characterised by a buildup of amyloid protein plaques in brain tissue.

In the course of their study, the researchers also discovered 13 other genes with possible links to AD which could potentially lead to the development of treatment for this disease.

Using SynaTate™, it can be seen that the potentially active region of CLU is on the third forward reading frame and searching this region using SynaSearch™ reveals significant homologies to clusterin in several different species. Having homologies to different species opens up doors for in vivo mutation studies of CLU expression in well known animal models such as mice.

SynaTate and SynaSearch can also be used to analyse the CR1 and PICALM genes.

Journal Reference: Nature Genetics

Click here, then click on .

On the results page, select the region that shows high SIGNIFICANCE by holding the left-click and dragging it across the entire selection as shown.

Right click inside the selected region to view options available.
Select Search nucleotide sequence.

Select Nucleotide-protein for the query type. Under the Target database panel, click on the dropdown menu bar and select Swiss-Prot UPKB Release 57.8.
Then click on the ‘Submit query‘ button.

The results show that the SIGNIFICANCE region of CLU matches clusterin which has homology in many species including the European rabbit (Oryctolagus cuniculus), horse (Equus caballus), dog (Canis familiaris) and mouse (Mus musculus).

To view the alignments in further detail, click on the individual scores next to the hit.