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

Abstract

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-β 1-42 (Aβ1-42), 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 Aβ1-40, Aβ1-42, 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. Aβ1-42 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 Aβ1-42/Aβ1-40 ratio showed a significant decrease in AD and MCI-AD as compared to MCI-MCI. Both Aβ1-42/t-tau and Aβ1-42/p-tau ratios showed significantly decreased values in AD and MCI-AD with respect to OND and MCI-MCI. Aβ1-42/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, rS = -0.71, p < 0.0001). Survival analysis showed that 81% of MCI with a low Aβ1-42/p-tau ratio (<1372) progressed to AD. The best model of logistic regression analysis retained Aβ1-42 and p-tau (sensitivity 75%, 95%CI: 70-80%; specificity 96%, 95%CI: 94-98%). We can conclude that Aβ1-42 and p-tau reliably predict conversion to AD in MCI patients.

Cerebrospinal Fluid Biomarkers Predict Clinical Evolution in Patients with Subjective Cognitive Decline and Mild Cognitive Impairment

“…They are also better predictors than clinical variables (MMSE and follow-up time) or genetic variables like the ε4 allele of the APOE gene, confirming previous studies [13,24,25]. The main reason why CSF compound scores are superior is that AD neuropathological changes, especially amyloidosis, may be incidentally present in controls or associated with other pathologies.…”

CSF and clinical hallmarks of subcortical dementias: focus on DLB and PDD

“…The decrease rate of p-tau-181 correlated with the MMSE decrease rate in AD subjects''. In line with the latter, Parnetti et al (2012) reinforced the predicting value of CSF biomarkers in identifying converter to AD, by following patients up to 4 years (''81 % of MCI with a low Ab1-42/p-tau ratio progressed to AD'', Parnetti et al 2012).…”

“…CSF biomarkers can predict the conversion from MCI to AD (Hansson et al 2006;Mattsson et al 2009;Blom et al 2009). Parnetti et al 2012 recently strengthened this point demonstrating that specific CSF biomarkers (the Ab1-42/ Ab1-40 ratio above all) indeed feature the so-called ''converters'' (AD and MCI-AD as compared to MCI-MCI). Landau et al (2010) concluded that, ''although baseline FDG-PET and episodic memory defaults better predict conversion to AD, p-tau(181p)/Abeta(1-42) ratio maintain its complimentary, but significant role in predicting longitudinal cognitive decline''.…”

Prediction of Mild Cognitive Impairment that Evolves into Alzheimer's Disease Dementia within Two Years using a Gene Expression Signature in Blood: A Pilot Study

“…Parnetti et al recently developed CSF biomarker models based on logistic regression analysis for the prediction of MCI that evolves into AD dementia within 2 years among individuals with MCI [57]. Using the CSF biomarkers A␤ 1-42 and p-tau for the model development, they obtained a sensitivity of 75% and specificity of 96%.…”