Increased cerebrospinal fluid levels of transforming growth factor-beta1 in Alzheimer's disease.
Accumulation of beta-amyloid (Abeta) in senile plaques in specific brain regions is a key event in the development of Alzheimer's disease (AD). Expression of transforming growth factor-beta1 (TGF-beta1), a regulator of brain responses to inflammation and injury, has been correlated with Abeta accumulation, aggregation and clearance in transgenic mice and increased production of amyloid precursor protein (APP) followed by Abeta generation in murine and human astrocyte cultures. Here, we compared TGF-beta1 levels in cerebrospinal fluid (CSF) from 20 AD patients and 20 healthy controls and correlated TGF-beta1 to intrathecal levels of the amyloidogenic 42-amino acid fragment of Abeta (Abeta42). AD patients had higher concentration of TGF-beta1 than controls (P = 0.002). Moreover, TGF-beta1 levels were negatively correlated to Abeta42 levels in the whole material (cases and controls, r = -0.35; P = 0.020), although this correlation failed to reach significance in the AD group alone (r = -0.38; P = 0.099). Taken together, the data indicate that TGF-beta1 plays a role in the processes that affect amyloid metabolism in AD.
Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg University, S-413 45 Gothenburg, Sweden. henrik.zetterberg@clinchem.gu.se
Henrik
H
Zetterberg
Niels
N
Andreasen
Kaj
K
Blennow
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D013053:Spectrophotometry / Q000379:methods; D016212:Transforming Growth Factor beta / Q000134:cerebrospinal fluid*; D053773:Transforming Growth Factor beta1; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C075222:amyloid beta-protein (1-42); D016875:tau Proteins