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Anomalously phosphorylated tau and Abeta fragments in the CSF correlates with cognitive impairment in MCI subjects.
Neurobiol Aging 2006; 27(2):237-44NA

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence of extracellular amyloid deposits, consisting largely of Abeta peptide and the presence of intraneuronal aggregates of neurofibillary tangles formed by tau. Development of cerebrospinal fluid (CSF) biomarkers has become a rapidly growing research field, considering the need for diagnostic tools for AD, thus allowing therapeutic compounds to have the greatest potential for being effective. We have focused on the relationships between critical biomarkers such as tau and Abeta in the CSF and the cognitive impairment of patients, as assessed by a battery of neuropsychological tests derived from CDR and CERAD, of value in the evaluation of AD patients. As part of a longitudinal study, we analyzed by ELISA and Western blots the levels and molecular patterns of hyperphosphorylated tau in the CSF of three different groups of patients: AD patients between 69- and 73-years-old, a group characterized with mild cognitive impairment (MCI) between 65- and 70-years-old, and a non-demented neurological control group of comparable ages. The levels of AT8-reactive phosphorylated tau were significantly higher (P<0.05) in AD patients (0.604+/-0.078, n=23) as compared with the control group (0.457+/-0.086, n=25). No differences between the levels of AT8-reactive tau of MCI patients (0.510+/-0.090, n=45) and controls were observed. However, when the MCI group was divided on the basis of the total box score (TBS) from CDR, those subjects with a TBS<1.5 presented tau levels (0.456+/-0.032, n=31) similar to controls, whereas those patients with TBS>or=1.5 displayed tau levels (0.590+/-0.086, n=14) comparable with those of AD. Western blot analyses revealed a higher AT8 reactivity in CSF samples of AD patients as compared with MCI and control samples, indicating higher levels of AD tau phosphoepitopes in the CSF. Tau heterogeneity was observed in samples of AD and MCI with higher impairment as compared with controls. As expected from previous reports, levels of Abeta (1-42) were lower (0.052+/-0.005) than controls (0.070+/-0.010), whereas the levels of MCI group were 0.060+/-0.007. The MCI group with a TBS>or=1.5 presented Abeta levels of 0.053+/-0.005 similar to those of AD patients, whereas the MCI group with TBS<1.5 exhibited Abeta levels (0.066+/-0.007) similar to controls. Studies highlight the relationships between anomalously phosphorylated tau markers in CSF with the information from TBS analysis of the different groups of patients.

Authors+Show Affiliations

Laboratory of Cellular, Molecular Biology and Neurosciences, Millennium Institute for Advanced Studies (CBB), Edificio Milenio, Las Encinas 3370, Nuñoa, Santiago, Chile. rmaccion@uchile.cl

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16399209

Citation

Maccioni, Ricardo B., et al. "Anomalously Phosphorylated Tau and Abeta Fragments in the CSF Correlates With Cognitive Impairment in MCI Subjects." Neurobiology of Aging, vol. 27, no. 2, 2006, pp. 237-44.
Maccioni RB, Lavados M, Guillón M, et al. Anomalously phosphorylated tau and Abeta fragments in the CSF correlates with cognitive impairment in MCI subjects. Neurobiol Aging. 2006;27(2):237-44.
Maccioni, R. B., Lavados, M., Guillón, M., Mujica, C., Bosch, R., Farías, G., & Fuentes, P. (2006). Anomalously phosphorylated tau and Abeta fragments in the CSF correlates with cognitive impairment in MCI subjects. Neurobiology of Aging, 27(2), pp. 237-44.
Maccioni RB, et al. Anomalously Phosphorylated Tau and Abeta Fragments in the CSF Correlates With Cognitive Impairment in MCI Subjects. Neurobiol Aging. 2006;27(2):237-44. PubMed PMID: 16399209.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anomalously phosphorylated tau and Abeta fragments in the CSF correlates with cognitive impairment in MCI subjects. AU - Maccioni,Ricardo B, AU - Lavados,Manuel, AU - Guillón,Marta, AU - Mujica,Cristina, AU - Bosch,Ruben, AU - Farías,Gustavo, AU - Fuentes,Patricio, Y1 - 2005/04/07/ PY - 2004/05/06/received PY - 2005/01/04/revised PY - 2005/01/10/accepted PY - 2006/1/10/pubmed PY - 2006/3/15/medline PY - 2006/1/10/entrez SP - 237 EP - 44 JF - Neurobiology of aging JO - Neurobiol. Aging VL - 27 IS - 2 N2 - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence of extracellular amyloid deposits, consisting largely of Abeta peptide and the presence of intraneuronal aggregates of neurofibillary tangles formed by tau. Development of cerebrospinal fluid (CSF) biomarkers has become a rapidly growing research field, considering the need for diagnostic tools for AD, thus allowing therapeutic compounds to have the greatest potential for being effective. We have focused on the relationships between critical biomarkers such as tau and Abeta in the CSF and the cognitive impairment of patients, as assessed by a battery of neuropsychological tests derived from CDR and CERAD, of value in the evaluation of AD patients. As part of a longitudinal study, we analyzed by ELISA and Western blots the levels and molecular patterns of hyperphosphorylated tau in the CSF of three different groups of patients: AD patients between 69- and 73-years-old, a group characterized with mild cognitive impairment (MCI) between 65- and 70-years-old, and a non-demented neurological control group of comparable ages. The levels of AT8-reactive phosphorylated tau were significantly higher (P<0.05) in AD patients (0.604+/-0.078, n=23) as compared with the control group (0.457+/-0.086, n=25). No differences between the levels of AT8-reactive tau of MCI patients (0.510+/-0.090, n=45) and controls were observed. However, when the MCI group was divided on the basis of the total box score (TBS) from CDR, those subjects with a TBS<1.5 presented tau levels (0.456+/-0.032, n=31) similar to controls, whereas those patients with TBS>or=1.5 displayed tau levels (0.590+/-0.086, n=14) comparable with those of AD. Western blot analyses revealed a higher AT8 reactivity in CSF samples of AD patients as compared with MCI and control samples, indicating higher levels of AD tau phosphoepitopes in the CSF. Tau heterogeneity was observed in samples of AD and MCI with higher impairment as compared with controls. As expected from previous reports, levels of Abeta (1-42) were lower (0.052+/-0.005) than controls (0.070+/-0.010), whereas the levels of MCI group were 0.060+/-0.007. The MCI group with a TBS>or=1.5 presented Abeta levels of 0.053+/-0.005 similar to those of AD patients, whereas the MCI group with TBS<1.5 exhibited Abeta levels (0.066+/-0.007) similar to controls. Studies highlight the relationships between anomalously phosphorylated tau markers in CSF with the information from TBS analysis of the different groups of patients. SN - 0197-4580 UR - https://www.unboundmedicine.com/medline/citation/16399209/Anomalously_phosphorylated_tau_and_Abeta_fragments_in_the_CSF_correlates_with_cognitive_impairment_in_MCI_subjects_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(05)00066-7 DB - PRIME DP - Unbound Medicine ER -