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Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype.
Dement Geriatr Cogn Disord 2009; 27(5):458-64DG

Abstract

BACKGROUND/AIMS

Increased cerebrospinal fluid (CSF) tau, decreased CSF amyloid-beta42 (Abeta42) and the apolipoprotein E gene (APOE) epsilon4 allele predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Here, we investigated these markers to assess their predictive value and influence on the rate of disease progression.

METHODS

Using ELISA, we measured the CSF biomarkers in 47 AD patients, 58 patients with MCI and 35 healthy control subjects. Twenty-eight MCI patients revisited the clinic and half of them progressed to AD during a period of 3-12 years.

RESULTS

The expected changes in CSF total (T)-tau, phosphorylated (P)-tau and Abeta42 levels were found in AD, confirming the diagnostic value of these biomarkers. We were also able to corroborate an increased risk for progression from MCI to AD with elevated CSF T-tau and P-tau and with the presence of the APOE epsilon4/epsilon4 genotype, but not with decreased Abeta42. Finally, for the first time we demonstrated that MCI subjects with high CSF T-tau or P-tau and APOE epsilon4 homozygosity progressed faster from MCI to AD.

CONCLUSIONS

CSF T-tau and P-tau as well as the APOE epsilon4/epsilon4 genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD.

Authors+Show Affiliations

Section of Molecular Geriatrics, Department of Public Health, Uppsala University, Uppsala, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19420940

Citation

Blom, Elin S., et al. "Rapid Progression From Mild Cognitive Impairment to Alzheimer's Disease in Subjects With Elevated Levels of Tau in Cerebrospinal Fluid and the APOE Epsilon4/epsilon4 Genotype." Dementia and Geriatric Cognitive Disorders, vol. 27, no. 5, 2009, pp. 458-64.
Blom ES, Giedraitis V, Zetterberg H, et al. Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype. Dement Geriatr Cogn Disord. 2009;27(5):458-64.
Blom, E. S., Giedraitis, V., Zetterberg, H., Fukumoto, H., Blennow, K., Hyman, B. T., ... Ingelsson, M. (2009). Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype. Dementia and Geriatric Cognitive Disorders, 27(5), pp. 458-64. doi:10.1159/000216841.
Blom ES, et al. Rapid Progression From Mild Cognitive Impairment to Alzheimer's Disease in Subjects With Elevated Levels of Tau in Cerebrospinal Fluid and the APOE Epsilon4/epsilon4 Genotype. Dement Geriatr Cogn Disord. 2009;27(5):458-64. PubMed PMID: 19420940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype. AU - Blom,Elin S, AU - Giedraitis,Vilmantas, AU - Zetterberg,Henrik, AU - Fukumoto,Hiroaki, AU - Blennow,Kaj, AU - Hyman,Bradley T, AU - Irizarry,Michael C, AU - Wahlund,Lars-Olof, AU - Lannfelt,Lars, AU - Ingelsson,Martin, Y1 - 2009/05/07/ PY - 2009/01/30/accepted PY - 2009/5/8/entrez PY - 2009/5/8/pubmed PY - 2009/8/13/medline SP - 458 EP - 64 JF - Dementia and geriatric cognitive disorders JO - Dement Geriatr Cogn Disord VL - 27 IS - 5 N2 - BACKGROUND/AIMS: Increased cerebrospinal fluid (CSF) tau, decreased CSF amyloid-beta42 (Abeta42) and the apolipoprotein E gene (APOE) epsilon4 allele predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Here, we investigated these markers to assess their predictive value and influence on the rate of disease progression. METHODS: Using ELISA, we measured the CSF biomarkers in 47 AD patients, 58 patients with MCI and 35 healthy control subjects. Twenty-eight MCI patients revisited the clinic and half of them progressed to AD during a period of 3-12 years. RESULTS: The expected changes in CSF total (T)-tau, phosphorylated (P)-tau and Abeta42 levels were found in AD, confirming the diagnostic value of these biomarkers. We were also able to corroborate an increased risk for progression from MCI to AD with elevated CSF T-tau and P-tau and with the presence of the APOE epsilon4/epsilon4 genotype, but not with decreased Abeta42. Finally, for the first time we demonstrated that MCI subjects with high CSF T-tau or P-tau and APOE epsilon4 homozygosity progressed faster from MCI to AD. CONCLUSIONS: CSF T-tau and P-tau as well as the APOE epsilon4/epsilon4 genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD. SN - 1421-9824 UR - https://www.unboundmedicine.com/medline/citation/19420940/Rapid_progression_from_mild_cognitive_impairment_to_Alzheimer's_disease_in_subjects_with_elevated_levels_of_tau_in_cerebrospinal_fluid_and_the_APOE_epsilon4/epsilon4_genotype_ L2 - https://www.karger.com?DOI=10.1159/000216841 DB - PRIME DP - Unbound Medicine ER -