title: HPA axis dysregulation associated to apolipoprotein E4 genotype in Alzheimer's disease.
abstract: The present work investigated the involvement of cortisol and its receptors, glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), in Alzheimer's disease (AD). Cortisol was measured in cerebrospinal fluid (CSF) samples from controls, mild cognitive impairment (MCI), progressive MCI evolving to AD, and AD. CSF cortisol levels do not seem to have a prognostic value, as increases in cortisol levels were found only in AD patients. GR expression was decreased while MR expression was increased in the frontal cortex of AD. When considering degeneration (ratio to synaptophysin and the post-synaptic marker PSD95), GR expression was similar between controls and AD, suggesting that GR loss was due to synaptic degeneration in AD. Increases in cortisol levels and MR expression were associated to an apolipoprotein E4 genotype. Cognitive status was negatively associated to CSF cortisol. In apolipoprotein E4 carriers, MR but not GR expression, negatively correlated to Mini-Mental Status Examination score and positively correlated to frontal cortex amyloid-β levels. It is concluded that there is a dysregulation of the hypothalamus-pituitary-adrenal axis in AD that seems to be consequence rather than cause of AD.
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Alzheimer's Disease Research Center, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Gil-Bea
authors.forename: Barbara
authors.initials: B
authors.lastname: Aisa
authors.forename: Alina
authors.initials: A
authors.lastname: Solomon
authors.forename: Maite
authors.initials: M
authors.lastname: Solas
authors.forename: Maria
authors.initials: M
authors.lastname: del Carmen Mugueta
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Miia
authors.initials: M
authors.lastname: Kivipelto
authors.forename: Angel
authors.initials: A
authors.lastname: Cedazo-Mínguez
authors.forename: María J
authors.initials: MJ
authors.lastname: Ramírez
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000134:cerebrospinal fluid / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers; D018161:Receptors, Mineralocorticoid; D006854:Hydrocortisone