Putative association of polymorphism in the mannose 6-phosphate receptor gene with major depression and Alzheimer's disease.

The endosomal lysosomal system might play a role in Alzheimer's disease, but its impact in major depression is unknown. The expression of the cation-dependent mannose 6-phosphate receptor (CD-MPR) is increased in Alzheimer's disease and the CD-MPR gene is located next to a region on chromosome 12 possibly linked to Alzheimer's disease. We investigated a C/T polymorphism in the CD-MPR gene in 188 Alzheimer's disease patients, in a control sample of 193 patients with major depression, as hospitalized controls, and in 259 healthy controls. We examined the interaction of the CD-MPR polymorphism with the putative risk factor for Alzheimer's disease, the cathepsin D T-allele. No significant association of the CD-MPR C-allele with Alzheimer's disease was observed. However, exploratory data analysis revealed an increased frequency of the CD-MPR C-allele in patients with major depression; thus, the C-allele may be a risk factor for depression. Gene location and function of the CD-MPR suggest an involvement in Alzheimer's disease; however, we could not find an association of the CD-MPR polymorphism with Alzheimer's disease. Since exploratory data suggest an involvement of the endosomal lysosomal system in major depression, further studies are warranted to investigate the biological role of the CD-MPR in major depression.