Plasma P-tau181 as a Marker of Progression to Alzheimer’s Disease Dementia in Subjective Cognitive Decline and Mild Cognitive Impairment.
Giulia Giacomucci1, Silvia Bagnoli1, Assunta Ingannato1, Chiara Crucitti1, Sonia Padiglioni2, Valentina Moschini2, Carmen Morinelli2, Salvatore Mazzeo3, Sandro Sorbi1, Benedetta Nacmias1, Valentina Bessi1
1Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, 2Research and Innovation Centre for Dementia-CRIDEM, AOU Careggi, 3Vita-Salute San Raffaele University
Objective:
To explore the prognostic role of plasma phosphorylated tau (p-tau) 181 levels in Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI) as a marker of progression along the continuum of cognitive decline.
Background:

In a future perspective of clinical application of plasma biomarkers, p-tau181 is becoming notable in prodromal stages of AD, as a valuable marker for tauopathy, one of the core features of AD. However, little is known about its prognostic value for progression of cognitive decline in early phases of AD.

Design/Methods:

We included 47 SCD, 43 MCI and 24 Alzheimer’s Disease demented (AD-d) patients, who underwent clinical evaluation, neuropsychological assessment, Apolipoprotein E (APOE) genotyping, plasma p-tau181 analysis with SiMoA assay and CSF biomarkers analysis (Aβ1-42, Aβ1-42/1-40, p-tau, t-tau). Forty patients (25 SCD, 9 MCI, 6 AD-d) underwent Amyloid PET. According to the Revised Criteria of Alzheimer’s Association Workgroup, patients were classified as Core1+ or Core1-. 

Results:

Plasma p-tau181 levels were significantly higher in SCD Core1+ than in SCD Core1- (2.75±0.75 vs 1.86±0.84, p=0.005, Cohen’s d=0.50) and in MCI Core1+ than MCI Core1- (3.36±1.42 vs 1.82±0.90, p<0.001, Cohen’s d=0.64). Plasma p-tau181 levels showed a high accuracy in discriminating Core1+ from Core1- patients (AUC=0.86, sensitivity 0.80, specificity 0.79). In a follow up time of 9.00±6.46 years, 9 out of 59 patients (1 SCD and 8 MCI) converted to AD dementia. Logistic regression analysis significantly predicted conversion to AD dementia, identifying plasma p-tau181 (OR=2.53, p=0.028) as significant predictor.

Conclusions:

Plasma p-tau181 showed a good accuracy in discriminating SCD and MCI patients classified as affected by AD according to new proposed criteria. Moreover, plasma p-tau181 levels seem to be a predictor of progression to AD dementia in SCD and MCI, thus being considered as an encouraging tool for the early detection of worsening of cognitive decline in early phases of AD.

10.1212/WNL.0000000000208530
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