Performance of Aβ1-40, Aβ1-42, Total Tau, and Phosphorylated Tau as Predictors of Dementia in a Cohort of Patients with Mild Cognitive Impairment

被引:81
作者
Parnetti, Lucilla [1 ]
Chiasserini, Davide [4 ]
Eusebi, Paolo [2 ]
Giannandrea, David
Bellomo, Gianni [3 ]
De Carlo, Claudia
Padiglioni, Chiara
Mastrocola, Sara
Lisetti, Viviana [4 ]
Calabresi, Paolo [4 ]
机构
[1] Univ Perugia, Neurol Clin, Ctr Disturbi Memoria, Unita Valutat Alzheimer,Osped S Maria della Miser, I-06132 Perugia, Italy
[2] Dipartimento Epidemiol Reg Umbria, Perugia, Italy
[3] Osped San Giovanni Battista, Foligno, Italy
[4] IRCCS Rome, Fdn S Lucia, Rome, Italy
关键词
Alzheimer's disease; amyloid-beta; 1-40; 1-42; biomarker; cerebrospinal fluid; dementia; mild cognitive impairment; phosphorylated tau; total tau; ALZHEIMERS ASSOCIATION WORKGROUPS; CEREBROSPINAL-FLUID BIOMARKERS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; FOLLOW-UP; DISEASE; CSF; RATIO; BETA-AMYLOID((1-42)); RECOMMENDATIONS;
D O I
10.3233/JAD-2011-111349
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Mild cognitive impairment (MCI) is a common condition in the elderly which may remain stable along time (MCI-MCI) or evolve into Alzheimer's disease (MCI-AD) or other dementias. Cerebrospinal fluid (CSF) classical biomarkers, i.e., amyloid-beta 1-42 (A beta(1-42)), total tau (t-tau), and phosphorylated tau (p-tau) reflect the neuropathological changes taking place in AD brains, thus disclosing the disease in its prodromal phase. With the aim to evaluate the power of each biomarker and/or their combination in predicting AD progression, we have measured CSF A beta(1-40), A beta(1-42), t-tau, and p-tau in patients with AD, MCI-MCI, MCI-AD, and other neurological diseases without dementia (OND) followed up for four years. A beta(1-42) levels were significantly lower in AD and MCI-AD than in MCI-MCI. T-tau and p-tau levels were significantly increased in AD and MCI-AD versus OND and MCI-MCI. The A beta(1-42)/A beta(1-40) ratio showed a significant decrease in AD and MCI-AD as compared to MCI-MCI. Both A beta(1-42)/t-tau and A beta(1-42)/p-tau ratios showed significantly decreased values in AD and MCI-AD with respect to OND and MCI-MCI. A beta(1-42)/p-tau ratio was the best parameter for discriminating MCI-AD from MCI-MCI (sensitivity 81%, specificity 95%), being also correlated with the annual change rate in the Mini Mental State Examination annual change rate score (MMSE-ACR, r(S)=-0.71, p<0.0001). Survival analysis showed that 81% of MCI with a low A beta(1-42)/p-tau ratio (<1372) progressed to AD. The best model of logistic regression analysis retained A beta(1-42) and p-tau (sensitivity 75%, 95%CI: 70-80%; specificity 96%, 95%CI: 94-98%). We can conclude that A beta(1-42) and p-tau reliably predict conversion to AD in MCI patients.
引用
收藏
页码:229 / 238
页数:10
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