We measured the levels of two beta-amyloid (Abeta)-sequestering proteins, apolipoprotein (Apo) E and transthyretin (TTR), in ventricular human cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients and controls in relation to brain histological findings. We also studied actin levels in CSF as a marker of the biochemical role of these two proteins in the cytoskeleton. We show that TTR levels in CSF were significantly decreased in AD patients compared to controls and negatively correlated with the senile plaque (SP) abundance. Moreover, actin levels were positively linked to TTR levels and increased in CSF samples of patients homozygous for the ApoE epsilon4-allele. We propose that TTR and ApoE4 may have competition in the aggregation of Abeta and its deposition in the SP of AD brain. The relationships between ApoE, TTR and actin could suggest a metabolic implication of ApoE genetics and TTR levels in cytoskeletal biochemistry which may be relevant to the pathogenesis of AD.