Alzheimer's Disease Diagnostic


Secreted Klotho protein sKL is mainly expressed in the CNS, in contrast to transmembrane Klotho, which makes sKL a more specific biomarker for neuronal disorders. sKL levels start to decrease at very early phases of AD, becoming a good biomarker for disease prognosis and progression.

We have demonstrated that low levels of sKL are associated with AD and aging. More important, we observed a significant decrease of sKL in the brain of 3xTg-AD animals, even before beta amyloid plaques appear or before cognitive impairments are evident.  We have also reported that sKL levels decline during progression of the Alzheimer’s disease (Fig 2) and also during the aging process in different brain regions associated with cognition as hippocampus or cortex. Taking into account the great potential of sKL as an early-stage biomarker, selective detection of its levels becomes an interesting strategy. Unfortunately, none of the Klotho antibodies currently available distinguishes between different klotho isoforms. To address this issue, our group has generated a new specific and sensitive antibody (Ab-K113) against sKL isoform.

Therefore, sKL biomarker could also be used for the efficacy evaluation and follow-up of treatments for neurodegenerative diseases. As a result, our team has generated specific antibodies against the sKL isoform of both, mice and humans. These antibodies have demonstrated high affinity and specificity, showing an excellent potential as diagnostic tools. Our present aim is to develop a sensitive ELISA kit, with special focus in the detection of sKL levels in samples obtained using the less invasive possible procedures.