ABSTRACT
Plasma, urine and cerebrospinal fluid (CSF) were examined for biochemical markers of dementia. Protein-conjugated acrolein (PC-Acro) and the amyloid-ß (Aß)40/42 ratio in plasma can be used to detect mild cognitive impairment (MCI) and Alzheimer's disease (AD). In plasma, PC-Acro and the Aß40/42 ratio in MCI and AD were significantly higher relative to non-demented subjects. Furthermore, urine acrolein metabolite, 3-hydroxypropyl mercapturic acid (3-HPMA)/creatinine (Cre) and amino acid-conjugated acrolein (AC-Acro)/Cre in AD were significantly lower than MCI. It was also shown that reduced urine 3-HPMA/Cre correlated with increased plasma Aß40/42 ratio in dementia. The Aß40/PC-Acro ratio in CSF, together with Aß40 and Aß40/42 ratio, was lower in AD than MCI. Increased plasma PC-Acro and Aß40/42 ratio and decreased urine 3-HPMA/Cre correlated with cognitive ability (MMSE). These results indicate that the measurements of acrolein derivatives together with Aß and Cre in biologic fluids is useful to estimate severity of dementia.
Subject(s)
Acrolein , Amyloid beta-Peptides , Creatinine , Dementia , Peptide Fragments , Acrolein/blood , Acrolein/cerebrospinal fluid , Acrolein/metabolism , Acrolein/urine , Amyloid beta-Peptides/blood , Amyloid beta-Peptides/cerebrospinal fluid , Amyloid beta-Peptides/metabolism , Amyloid beta-Peptides/urine , Animals , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Biomarkers/urine , Creatinine/blood , Creatinine/cerebrospinal fluid , Creatinine/metabolism , Creatinine/urine , Dementia/blood , Dementia/cerebrospinal fluid , Dementia/urine , Humans , Peptide Fragments/blood , Peptide Fragments/cerebrospinal fluid , Peptide Fragments/metabolism , Peptide Fragments/urineABSTRACT
BACKGROUND: We found previously that the amyloid ß40/42 (Aß40/42) ratio and the level of protein-conjugated acrolein (PC-Acro) in plasma were increased in mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects. We determined whether MCI and AD subjects can be differentiated based on the levels of Aß40, Aß42, and PC-Acro in cerebrospinal fluid (CSF). METHODS: Aß40, Aß42, PC-Acro, Tau and phosphorylated Tau in CSF were measured by ELISA. RESULTS: Median values of Aß40, Aß40/PC-Acro and Aß40/42 in CSF were significantly lower in 54 AD subjects than those in 40 MCI subjects. Severity of VOI (volume of interest) atrophy was most intensely correlated with the decrease in Aß40/PC-Acro and then that in Aß40 and Aß42/PC-Acro. MMSE was most intensely correlated with the decrease in Aß42 and Aß40, and then that in Aß42/PC-Acro and Aß40/PC-Acro. CONCLUSION: A decrease in Aß40/PC-Acro in CSF is well correlated with brain damage, and a decrease in Aß42 and Aß40 is well correlated with cognitive ability. Measurement of PC-Acro together with Aß40 and Aß42 provides a more precise evaluation of severity of AD subjects.
