Reduced TNF-α and increased IGF-I levels in the serum of Alzheimer's disease patients treated with the neurotrophic agent Cerebrolysin

Abstract

According to current scientific knowledge, excess tumour necrosis factor-α (TNF-α) and low insulin-like growth factor-I (IGF-I) are pathogenic-risk factors that constitute therapeutic targets for Alzheimer's disease (AD). Changes in serum TNF-α, total and dissociable IGF-I levels were determined by ELISA in 207 AD patients completing a 24-wk, double-blind, placebo-controlled trial to evaluate the effects of the neurotrophic compound Cerebrolysin (Cere: 10, 30 or 60 ml for 12 wk). At week 24, Cere reduced TNF-α and enhanced dissociable IGF-I with respect to placebo in a dose-related manner. TNF-α decreased in parallel with behavioural disturbances. Increases in total IGF-I were induced by 60 ml Cere and correlated significantly with improvements in global function, disabilities and behaviour in late-onset AD patients. These results showing for the first time the opposite influence of one anti-dementia treatment on serum TNF-α and IGF-I suggest the contribution of both factors to the clinical effects of Cere, and probably other drugs.

Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats

“…Another merit to CBL is its ability to reduce TNF-α, an event shown in this study, and one pivotal factor for central neuronal death [55]. Directly, CBL is reported to reduce TNF-α [36] and indirectly via reduction of BBB permeability [56] thus limiting entry of TNF-α into the brain, which further contributes to halting excess NO production and tissue injury reflected as behavioral improvement in the current work.…”

“…Notably, in the current investigation, STZ administration increased serum TNF-α that inhibits the uptake of circulating free fatty acids and accelerates lipolysis in adipose tissue [35], thus lending a plausible explanation for the reduction in body weight; both former events were impeded by CBL administration in the present work. The anti-inflammatory effect of CBL is supported by the work of Alvarez et al [36], who reported decreased TNF-α level in Alzheimer's patients.…”

Persistence of the effects of Cerebrolysin on cognition and qEEG slowing in vascular dementia patients: Results of a 3-month extension study

“…Because qEEG activity correlates with cerebral glucose metabolism in VaD patients [23] and Cerebrolysin upregulates the expression of the blood-brain barrier GLUT1 glucose transporter [24], a long-term influence of Cerebrolysin on the brain's glucose supply could represent an alternative mechanism by which to maintain the reduction of qEEG slowing in patients with VaD. According to recent studies showing that 30 mL of Cerebrolysin reduces serum TNF-α levels significantly in AD patients after 12 weeks without treatment [15] and that short interfering RNAs targeting TNF-α are able to reduce its expression in the rat somatosensory cortex and decrease EEG delta wave power [9], it is also possible that an inhibitory effect of Cerebrolysin on brain TNF-α might account for the decrease of delta activity produced by this compound in VaD.…”

“…The data were normalised, and relative power (%) was used as the reference parameter. The following frequency bands were studied: delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12 Hz) and beta (12)(13)(14)(15)(16). These frequency bands were selected in accordance with those used in previous studies conducted with Cerebrolysin in traumatic brain injury and vascular dementia [10].…”

“…Experimental studies demonstrated that Cerebrolysin reduces brain amyloid-beta production by inhibiting the activity of Cdk-5 and GSK-3β kinases in transgenic mice, and it decreases neuro-inflammation in vitro and in vivo [13,14]. Recently, it has also been found that Cerebrolysin reduces the circulating levels of TNF-α in a dose-dependent manner in patients with AD [15].…”