GROWTH FACTORS DECREASE IN SUBJECTS WITH MILD TO MODERATE ALZHEIMER'S DISEASE (AD): POTENTIAL CORRECTION WITH DEHYDROEPIANDROSTERONE-SULPHATE (DHEAS)

Abstract The integrity of neuroprotection is an important component against the development of cognitive disorders and AD. Within this context, DHEAS would seem to have some positive metabolic and endocrine effects to delay brain aging by recovering the impairment of neuroprotective growth factors....

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Published in:	Archives of gerontology and geriatrics Vol. 49; pp. 173 - 184
Main Authors:	Luppi, C, Fioravanti, M, Bertolini, B, Inguscio, M, Grugnetti, A, Guerriero, F, Rovelli, C, Cantoni, F, Guagnano, P, Marazzi, E, Rolfo, E, Ghianda, D, Levante, D, Guerrini, C, Bonacasa, R, Solerte, S.B
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Ireland Ltd 2009
Subjects:	Aged Alzheimer Disease - blood Alzheimer Disease - drug therapy Alzheimer's disease Biomarkers - blood Blood Dehydroepiandrosterone Sulfate - administration & dosage Dehydroepiandrosterone Sulfate - therapeutic use Dehydroepiandrosterone-sulphate (DHEAS) Dementia Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Female Follow-Up Studies Glucose Growth hormones Humans Insulin-Like Growth Factor I - metabolism Insulin-like growth factor-1 (IGF-1) Intercellular Signaling Peptides and Proteins - blood Internal Medicine Male Natural killer cells Neuroprotection Stimulation Transforming Growth Factor beta1 - blood Transforming growth factor-(β1 (TGF(β1) Treatment Outcome Vascular endothelial growth factor (VEGF) Vascular Endothelial Growth Factor A - blood Neuroprotection Vascular endothelial growth factor (VEGF) Insulin-like growth factor-1 (IGF-1) Natural killer cells Dehydroepiandrosterone-sulphate (DHEAS) Alzheimer's disease Transforming growth factor-(β1 (TGF(β1) Dementia
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Summary:	Abstract The integrity of neuroprotection is an important component against the development of cognitive disorders and AD. Within this context, DHEAS would seem to have some positive metabolic and endocrine effects to delay brain aging by recovering the impairment of neuroprotective growth factors. In the present study we measured by ELISA the secretion of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and transforming growth factor-β1 (TGFβ1) in the supernatants of cultured circulating peripheral blood mononuclear cells (PBMC) from which natural killer cells (NK) were separated (PBMC-NK) (pg/ml/7.75 × 106 cells) in healthy subjects and in age-matched patients with mild to moderate AD. The growth factors were measured in spontaneous conditions and after stimulation with growth hormone (GH) 1 μg/ml (IGF-1), lipopolysaccharide (LPS) 1 μg/ml (VEGF) and glucose 10 μM (TGF(β1). AD group demonstrated at baseline a severe reduction of IGF-1 (3.7 + 1.2 pg/ml after GH), VEGF (63 ± 18 pg/ml spontaneous and 210 ± 65 pg/ml after LPS) and TGF(β1 (33 ± 10 pg/ml spontaneous and 75 ± 12 pg/ml after glucose) secretions compared to healthy elderly subjects (IGF-1, 9.5 ± 2.8 pg/ml after GH, p < 0.001; VEGF, 117 ± 38 pg/ml spontaneous, p < 0.001 and 690 ± 120 pg/ml after LPS, p < 0.001; and TGF(β1, 73 ± 21 pg/ml spontaneous, p < 0.001 and 169 ± 53 pg/ml after glucose, p < 0.001). Significant positive correlations between IGF-1 and VEGF concentrations were found both in healthy subjects (r = 0.87, p < 0.001) and in AD subjects (r = 0.87, p < 0.001). The co-incubation of NK cells with DHEAS (106 M/ml/cells) significantly increase IGF-1, VEGF and TGF (β1 production, reaching in AD group the normal concentrations found in healthy subjects (IGF-1, 7.9 + 2.4 pg/ml after GH; VEGF, 105 ± 31 pg/ml spontaneous and 670 ± 112 pg/ml after LPS; and TGFfβ1, 68 ± 18 pg/ml spontaneous and 155 ± 48 pg/ml after glucose). These data suggested that DHEAS is able to increase the immunoendocrine production of neuroprotective growth factors, which is reduced in AD subjects, so suggesting a new approach in the treatment of dementia.
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ISSN:	0167-4943 1872-6976
DOI:	10.1016/j.archger.2009.09.027