Reduced TNF-α and increased IGF-I levels in the serum of Alzheimer's disease patients treated with the neurotrophic agent cerebrolysin.
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.
Alvarez
X Anton
XA
Department of Neuropharmacology, EuroEspes Biomedical Research Centre, A Coruna, Spain. xantonal@yahoo.es
Sampedro
Carolina
C
Cacabelos
Ramon
R
Linares
Carlos
C
Aleixandre
Manuel
M
García-Fantini
Manuel
M
Moessler
Herbert
H
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D000596:Amino Acids / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D003071:Cognition / Q000187:drug effects; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000627:therapeutic use*; D015990:Placebo Effect; D012720:Severity of Illness Index; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D015854:Up-Regulation
D000596:Amino Acids; D015415:Biomarkers; D018697:Nootropic Agents; D014409:Tumor Necrosis Factor-alpha; C006952:cerebrolysin; D007334:Insulin-Like Growth Factor I