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This work was supported by the following grants to JV: Foundation Gent per Gent and SAF2010-19498 from the Spanish Ministry of Education and Science (MEC) co-financed with European FEDER funds; ISCIII2006-RED13-027 from the "Red Tematica de investigacion cooperativa en envejecimiento y fragilidad (RETICEF), and EU Funded COSTB35 and Prometeo 2010/074 from the Generalitat Valenciana. EG was beneficiary of a Juan de la Cierva grant number 405 2010-MICINN. The technical support of Ms. Alicia Peris is gratefully acknowledged.

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Lymphocytes from Young Healthy Persons Carrying the ApoE4 Allele Overexpress Stress-Related Proteins Involved in the Pathophysiology of Alzheimer's Disease

Publicado en:Journal Of Alzheimers Disease. 33 (1): 77-83 - 2013-01-01 33(1), DOI: 10.3233/jad-2012-120973

Autores: Badia, Mari-Carmen; Lloret, Ana; Giraldo, Esther; Dasi, Francisco; Olaso, Gloria; Alonso, Maria-Dolores; Vina, Jose

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Apolipoprotein E4 (ApoE4) is a major genetic risk factor for the development of Alzheimer's disease (AD). The aim of this work was to find if carrying ApoE4 alleles correlates with molecular changes associated with specific processes involved in AD pathophysiology and whether they are useful as early biomarkers of AD. Fifty four young healthy adults (aged 20-55) were recruited. Of these, 33 carried at least one ApoE4 allele and 21 did not (ApoE 3/3). We also recruited eleven patients with clinical diagnoses of probable AD and nine persons of similar age without dementia who served as controls of the AD patients. Using peripheral lymphocytes, we measured RNA expression of glycogen synthase kinase 3 beta (GSK3 beta), the regulator of calcineurin 1 (RCAN1), calcineurin, and RNA-dependent protein kinase (PKR) by PCR and protein levels of RCAN1, calcineurin, GSK3 beta, and phospho-tau by western blotting. Young healthy persons carrying the ApoE 4/4 genotype express more RNA for RCAN1, calcineurin, and PKR and higher protein levels of calcineurin, RCAN1, GSK3 beta, and phospho-tau than controls (ApoE 3/3). Moreover, we found that carrying one or two alleles for ApoE4 is associated with subjective cognitive impairment. We conclude that lymphocytes from young, non-demented persons carrying the ApoE 4/4 genotype show molecular changes that are involved in specific processes associated with the pathophysiology ofADsuch as increased phosphorylation of tau or increased expression of stress-related proteins like calcineurin, GSK3 beta, or RCAN1. These changes may help to understand the development of AD and in the early diagnosis of the disease.

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