Rapid Progression from Mild Cognitive Impairment to Alzheimer’s Disease in Subjects with Elevated Levels of Tau in Cerebrospinal Fluid and the <i>APOE </i>ε<i>4</i>/ε<i>4</i> Genotype

Dementia and Geriatric Cognitive Disorders - Tập 27 Số 5 - Trang 458-464 - 2009
Elin Blom1, Vilmantas Giedraitis1, Henrik Zetterberg2, Hiroaki Fukumoto3, Kaj Blennow2, Bradley T. Hyman3, Michael C. Irizarry3, Lars‐Olof Wahlund4, Lars Lannfelt1, Martin Ingelsson1
1Section of Molecular Geriatrics, Department of Public Health, Uppsala University, Uppsala,
2Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
3Alzheimer's Disease Research Unit, Massachusetts General Hospital-East, Charlestown, Mass., USA
4Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden

Tóm tắt

<i>Background/Aims:</i> Increased cerebrospinal fluid (CSF) tau, decreased CSF amyloid-β42 (Aβ42) and the apolipoprotein E gene <i>(APOE) </i>ε<i>4</i> 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. <i>Methods:</i> 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. <i>Results:</i> 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 <i>APOE </i>ε<i>4/</i>ε<i>4</i> 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 <i>APOE </i>ε<i>4</i> homozygosity progressed faster from MCI to AD. <i>Conclusions:</i> CSF T-tau and P-tau as well as the <i>APOE </i>ε<i>4/</i>ε<i>4</i> genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD.

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Dementia and Geriatric Cognitive Disorders

Tập 27 Số 5

458-464

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