ACTIVITY-DEPENDENT NEUROPROTECTIVE PROTEIN (ADNP): MARKING ALZHEIMER'S DISEASE AND SCHIZOPHRENIA

Activity-dependent neuroprotective protein (ADNP) is essential for brain formation, constituting part of the chromatin remodeling complex, SWI/SNF. Our recent findings associated ADNP with the autophagy, a process preserving the balance between synthesis, degradation and recycling of cellular components. The proteins, beclin1 and microtubule associated protein 1 light chain 3 (LC3) regulate the autophagy process. We showed that ADNP haploinsufficiency in mice, which results in Alzheimer's disease (AD)-like tauopathy and cognitive dysfunction, exhibited reduced hippocampal beclin1. At the protein level, ADNP co-immunoprecipitated with LC3B suggesting a direct association with the autophagy process. Autophagy is deregulated in AD and we have recently shown deregulation of autophagy in schizophrenia. Furthermore, ADNP transcripts were increased in lymphocyted from schizophrenia patients compared to matched controls (Molecular Psychiatry, 2013, [Epub ahead of print]). The aim of the present project was to evaluate ADNP and the related ADNP2 lymphocyte expression in AD. Peripheral lymphocytes were isolated from AD patients and age-matched controls by ficoll grandiet separation. RNA was extracted using the Trizol reagent followed by reverse transcription and quantitative real time polymerase chain reaction (PCR) for ADNP and ADNP2 RNA. Results were normalize to the TATA box transcript. ADNP RNA was increased by ∼8-folds in AD lymphocyte samples compared to controls (p<0.05). This was in contrast to the transcript of ADNP2, which did not change. In comparison to schizophrenia patients (Molecular Psychiatry, 2013, [Epub ahead of print]), the increase in ADNP expression was apparently ∼3-fold greater in AD patients, and ADNP2 expression was also significantly increased in schizophrenia patients. Our results posit ADNP and ADNP2 lymphocyte expression as markers for AD and schizophrenia with differential disregulated expression in the two indications. Interestingly, previous proteomic studies identified ADNP as the only protein decreasing in AD serum, suggesting potential rapid turn-over, structural changes and/or defective translation mechanism that have been associated with cognitive deficiencies. These studies pave the path to better disease understanding, novel biomarkers and personalized medicine.