Dementia of the Alzheimer type and hypothalamus-pituitary-adrenocortical axis: changes in cerebrospinal fluid corticotropin releasing factor and plasma cortisol levels

Martignoni, E.; Petraglia, Felice; Costa, Alfredo; Bono, Giorgio; Genazzani, Ar; Nappi, Giuseppe

doi:10.1111/j.1600-0404.1990.tb00994.x

Cited by 73 publications

(23 citation statements)

References 29 publications

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“…55 Plasma cortisol levels reflect the degree of cognitive impairment in AD, 56 are associated with the presence of the APOE4 allele, 57 and correlate with Aβ-plaque brain burden measured by Pittsburgh compound B–labeled PET. 58 High cortisol levels were also reported previously in plasma, serum, or CSF in patients with MCI and AD compared with controls 56,59,60 and are also associated with more rapidly increasing symptoms of dementia. 56,60 Apolipoproteins have been implicated in the cause of AD, 61–63 and low levels of plasma ApoA-II are associated with an increased risk for cognitive decline in cognitively normal individuals.…”

Section: Discussionsupporting

confidence: 63%

Combined Plasma and Cerebrospinal Fluid Signature for the Prediction of Midterm Progression From Mild Cognitive Impairment to Alzheimer Disease

et al. 2016

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Section: Discussionsupporting

confidence: 63%

Combined Plasma and Cerebrospinal Fluid Signature for the Prediction of Midterm Progression From Mild Cognitive Impairment to Alzheimer Disease

et al. 2016

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“…HPA axis abnormalities are well described as underlying features of a number of neuropsychiatric and neurodegenerative conditions, including major depression (3), posttraumatic stress disorder (4), social phobia (5), Huntington disease (6), and Alzheimer’s disease (7). These abnormalities may influence susceptibility to disease states (8) or contribute to the severity of clinical symptoms (9).…”

mentioning

confidence: 99%

Genome-Wide Identification of Basic Helix–Loop–Helix and NF-1 Motifs Underlying GR Binding Sites in Male Rat Hippocampus

et al. 2017

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Glucocorticoids regulate hippocampal function in part by modulating gene expression through the glucocorticoid receptor (GR). GR binding is highly cell type specific, directed to accessible chromatin regions established during tissue differentiation. Distinct classes of GR binding sites are dependent on the activity of additional signal-activated transcription factors that prime chromatin toward context-specific organization. We hypothesized a stress context dependency for GR binding in hippocampus as a consequence of rapidly induced stress mediators priming chromatin accessibility. Using chromatin immunoprecipitation sequencing to interrogate GR binding, we found no effect of restraint stress context on GR binding, although analysis of sequences underlying GR binding sites revealed mechanistic detail for hippocampal GR function. We note enrichment of GR binding sites proximal to genes linked to structural and organizational roles, an absence of major tethering partners for GRs, and little or no evidence for binding at negative glucocorticoid response elements. A basic helix–loop–helix motif closely resembling a NeuroD1 or Olig2 binding site was found underlying a subset of GR binding sites and is proposed as a candidate lineage-determining transcription factor directing hippocampal chromatin access for GRs. Of our GR binding sites, 54% additionally contained half-sites for nuclear factor (NF)-1 that we propose as a collaborative or general transcription factor involved in hippocampal GR function. Our findings imply a dose-dependent and context-independent action of GRs in the hippocampus. Alterations in the expression or activity of NF-1/basic helix–loop–helix factors may play an as yet undetermined role in glucocorticoid-related disease susceptibility and outcome by altering GR access to hippocampal binding sites.

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“…Age and sex were known confounders affecting the HPA axis and the HP gonadal axis, with studies demonstrating an accentuated cortisol response in older women (Otte et al, 2005). We adjusted for total (Davis et al, 1986;Martignoni et al, 1990) and cognition (Echouffo-Tcheugui et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…While cortisol levels increase with physiological aging (Ferrari et al, 1995;Ferrari et al, 2004), multiple neuropsychiatric conditions demonstrate elevated cortisol levels irrespective of age. For example, cortisol levels are higher than normal in conditions such as schizophrenia, bipolar disorder (Gallagher et al, 2007;Ryan et al, 2004), major depression (Linkowski et al, 1987;Plotsky et al, 1995) and Alzheimer's disease (Davis et al, 1986;Martignoni et al, 1990). Within these conditions, cortisol levels are higher in those with a greater degree of cognitive impairment (Hinterberger et al, 2013;Zvěřová et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Elevated plasma cortisol associated with larger ventricles and smaller hippocampal volumes – a study in 2 independent elderly cohorts

Rajagopalan

Nho

Risacher

et al. 2020

Preprint

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170/170 words Number of Display Items: 4 (3 Figures and 1 Table)References: 60 Highlights:• Elevated cortisol associated with larger ventricular volumes and smaller hippocampal volumes• Associations are predominantly noted in the right cerebral hemisphere.• Similar non-significant trends noted in amygdalar volumes• Cortisol and stress reducing strategies may halt brain changes and improve quality of life • Imaging biomarkers may help assess efficacy of cortisol-lowering therapeutic interventions AbstractCortisol is considered the most fundamental stress hormone and is elevated in stress and multiple neuropsychiatric conditions. Prior studies have shown associations of plasma cortisol levels with total cerebral and hippocampal volumes and less consistently with the amygdala. Here, we extend our hypothesis to test associations of plasma cortisol with 1) ventricular 2) hippocampal and 3) amygdalar volumes, in two independent elderly cohorts across a broad cognitive spectrum ranging from normal cognition to Alzheimer's disease.We demonstrate elevated cortisol to be associated with larger lateral ventricular volumes and smaller hippocampal volumes, predominantly in the right cerebral hemisphere, regardless of age, sex or cognitive status. We noted a non-significant trend of smaller amygdalar volumes with elevated cortisol.Our findings support smaller brain parenchyma volumes seen with elevated cortisol and may encourage effective strategies reducing cortisol and stress. They may also serve as imaging biomarkers for assessing therapeutic benefits of stress and cortisol lowering interventions aiming to halt or reverse the brain volume alterations and theoretically improve cognition and quality of life.

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Dementia of the Alzheimer type and hypothalamus-pituitary-adrenocortical axis: changes in cerebrospinal fluid corticotropin releasing factor and plasma cortisol levels

Cited by 73 publications

References 29 publications

Combined Plasma and Cerebrospinal Fluid Signature for the Prediction of Midterm Progression From Mild Cognitive Impairment to Alzheimer Disease

Combined Plasma and Cerebrospinal Fluid Signature for the Prediction of Midterm Progression From Mild Cognitive Impairment to Alzheimer Disease

Genome-Wide Identification of Basic Helix–Loop–Helix and NF-1 Motifs Underlying GR Binding Sites in Male Rat Hippocampus

Elevated plasma cortisol associated with larger ventricles and smaller hippocampal volumes – a study in 2 independent elderly cohorts

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