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. 2009;27(5):458-64.
doi: 10.1159/000216841. Epub 2009 May 7.

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

Elin S Blom  1 , Vilmantas Giedraitis, Henrik Zetterberg, Hiroaki Fukumoto, Kaj Blennow, Bradley T Hyman, Michael C Irizarry, Lars-Olof Wahlund, Lars Lannfelt, Martin Ingelsson
Affiliations

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

Elin S Blom et al. Dement Geriatr Cogn Disord. 2009.

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.

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Figures

Fig. 1
Fig. 1
Levels of CSF biomarkers in AD patients, individuals with MCI and healthy controls (C). Levels of T-tau (a) and P-tau (b) were increased, whereas levels of Aβ42 (c) were decreased in AD patients compared to controls and MCI subjects (p < 0.01 for all). d Levels of Aβ40 did not differ between the diagnostic groups.
Fig. 2
Fig. 2
Levels of CSF biomarkers at baseline in individuals with MCI progressing to AD and those who remained stable during the follow-up. Both T-tau (a) and P-tau (b) levels were increased at baseline in individuals progressing to AD (p < 0.01 for both). An increase was also observed for Aβ40 (p < 0.05; d), whereas there was no difference in Aβ42 levels (c).
Fig. 3
Fig. 3
The MCI subjects who revisited the clinic were divided into 2 groups of equal size according to their levels of CSF P-tau. The group with the higher levels was found to have a significantly higher incidence of AD and a shorter time to progression compared to the group with the lower levels (p < 0.01).
See this image and copyright information in PMC

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