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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 ε44 Genotype

Blom E.S.a · Giedraitis V.a · Zetterberg H.b · Fukumoto H.c · Blennow K.b · Hyman B.T.c · Irizarry M.C.c · Wahlund L.-O.d · Lannfelt L.a · Ingelsson M.a
aSection of Molecular Geriatrics, Department of Public Health, Uppsala University, Uppsala, bDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; cAlzheimer’s Disease Research Unit, Massachusetts General Hospital-East, Charlestown, Mass., USA; dDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden Dement Geriatr Cogn Disord 2009;27:458–464 (DOI:10.1159/000216841)


Background/Aims: Increased cerebrospinal fluid (CSF) tau, decreased CSF amyloid-β42 (Aβ42) and the apolipoprotein E gene (APOE) ε4 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 Aβ42 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 ε4/ε4 genotype, but not with decreased Aβ42. Finally, for the first time we demonstrated that MCI subjects with high CSF T-tau or P-tau and APOE ε4 homozygosity progressed faster from MCI to AD. Conclusions: CSF T-tau and P-tau as well as the APOE ε4/ε4 genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD.


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