Performance of Aβ_1-40, Aβ_1-42, Total Tau, and Phosphorylated Tau as Predictors of Dementia in a Cohort of Patients with Mild Cognitive Impairment

Article type: Research Article

Authors: Parnetti, Lucilla^{a; *; 1} | Chiasserini, Davide^{a; d; 1} | Eusebi, Paolo^b | Giannandrea, David^a | Bellomo, Gianni^c | De Carlo, Claudia^a | Padiglioni, Chiara^a | Mastrocola, Sara^a | Lisetti, Viviana^{a; d} | Calabresi, Paolo^{a; d}

Affiliations: [a] Clinica Neurologica, Università degli Studi di Perugia, Perugia, Italy | [b] Dipartimento di Epidemiologia – Regione Umbria, Perugia, Italy | [c] Ospedale S.Giovanni Battista, Foligno, Italy | [d] Fondazione S. Lucia, I.R.C.C.S. Rome, Italy

Correspondence: [*] Correspondence to: Lucilla Parnetti, MD, PhD, Clinica Neurologica, Centro Disturbi della Memoria, Unità Valutativa Alzheimer, Università degli Studi di Perugia, Ospedale S. Maria della Misericordia, 06132 Perugia, Italy. Tel.: +39 075 578 3545; Fax: +39 075 578 4229; -mail: [email protected].

Note: [1] These authors equally contributed to the work.

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.

Keywords: Alzheimer's disease, amyloid-β 1-40, amyloid-β 1-42, biomarker, cerebrospinal fluid, dementia, mild cognitive impairment, phosphorylated tau, total tau

DOI: 10.3233/JAD-2011-111349

Journal: Journal of Alzheimer's Disease, vol. 29, no. 1, pp. 229-238, 2012