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P4‐277: CHANGES IN BRAIN NETWORK MEASURES IN PRE‐SYMPTOMATIC ALZHEIMER'S DISEASE WITH E280A PRESENILIN‐1 MUTATION GENE
Author(s) -
Tobon Carlos,
Duque Jon Edinson,
Ochoa John Fredy,
Hernandez Mauricio,
Quiroz Yakeel T.,
Lopera Francisco
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.07.047
Subject(s) - electroencephalography , clustering coefficient , presenilin , asymptomatic carrier , asymptomatic , audiology , statistics , mathematics , psychology , physics , medicine , disease , neuroscience , alzheimer's disease , cluster analysis
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. Methods: 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. Results: ADNP RNAwas increased by w8-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 w3-fold greater in AD patients, and ADNP2 expression was also significantly increased in schizophrenia patients. Conclusions: 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.