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Review
. 2024 Nov 30;25(23):12916.
doi: 10.3390/ijms252312916.

Role of Blood P-Tau Isoforms (181, 217, 231) in Predicting Conversion from MCI to Dementia Due to Alzheimer's Disease: A Review and Meta-Analysis

Gemma Lombardi  1   2 , Silvia Pancani  2 , Riccardo Manca  3   4 , Micaela Mitolo  3   5 , Simone Baiardi  6 , Federico Massa  7   8 , Luigi Coppola  9 , Monica Franzese  9 , Emanuele Nicolai  9 , Franca Rosa Guerini  10 , Roberta Mancuso  10 , Cristina Agliardi  10 , Simone Agostini  10 , Matteo Pardini  7   8 , Gianni Virgili  1 , Sandro Sorbi  1   2 , Piero Parchi  5   6 , Benedetta Nacmias  1 , Annalena Venneri  3   4
Affiliations
Review

Role of Blood P-Tau Isoforms (181, 217, 231) in Predicting Conversion from MCI to Dementia Due to Alzheimer's Disease: A Review and Meta-Analysis

Gemma Lombardi et al. Int J Mol Sci. .

Abstract

Blood-based biomarkers are minimally invasive tools to detect the pathological changes of Alzheimer's Disease (AD). This meta-analysis aims to investigate the use of blood-derived p-tau isoforms (181, 217, 231) to predict conversion from mild cognitive impairment (MCI) to AD dementia (ADD). Studies involving MCI patients with data on blood p-tau isoforms at baseline and clinical diagnosis at follow-up (≥1 year) were included. Twelve studies on p-tau 181 (4340 MCI, conversion rate 20.6%), four on p-tau 217 (913 MCI, conversion rate 33.4%), and one on p-tau 231 (135 MCI, conversion rate 33%) were included. For p-tau 181, the pooled area under the receiver operating characteristic curve (AUC) was 0.73 (95% CI = 0.68-0.78), and for p-tau 217 was 0.85 (95% CI = 0.75-0.91). Plasma levels of p-tau 181 had good discriminatory power to identify MCI patients who will convert to ADD. Although only four studies on p-tau 217 have been included in the meta-analysis, in the last year the predictive power of p-tau 217 is emerging as superior to that of other isoforms. However, given the high heterogeneity detected in the p-tau 217 studies included in this meta-analysis, additional supportive evidence is needed. Insufficient results were available for p-tau 231. These findings support the prognostic utility of p-tau 181 and p-tau 217 measured in blood to predict progression to ADD in MCI and encourage its future implementation in clinical practice.

Keywords: Alzheimer’s disease; biomarkers; blood; mild cognitive impairment; p-tau; plasma.

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Conflict of interest statement

FM received speaker honoraria from Roche Diagnostic S.p.A and Eli Lilly S.p.A. Authors LC, MF, and EN were employed by the company SYNLAB. The remaining authors (GL, SB, RM, MM, GV, SP, FG, RMa, CA, SA, MP, PP, BN, SS and AV) declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The flow chart of the literature selection.
Figure 2
Figure 2
Forest plot for blood p-tau 181 of the SMD of the individual studies and their respective weight. A positive SMD indicates higher p-tau 181 values in participants who converted to ADD. The results of component studies are shown as squares centred on the point estimate of the result of each study. The horizontal line runs through the square to show its confidence interval. The overall estimate from the meta-analysis and its confidence interval are put at the bottom, represented as a diamond. The centre of the diamond represents the pooled point estimate, and its horizontal tips represent the confidence interval. The solid line is on 0 and corresponds to an equivalence between mean p-tau 181 value in MCI converters and non-converters to ADD; the dashed line is on the overall meta-analytic pooled-estimate on the SMD scale (that is 0.85). All studies [30,31,56,57,59,60,61,62,63,64,65] were beyond the 0 line except for Park 2024 [66]. Legend: size: sample size (number); FU: follow-up (years).
Figure 3
Figure 3
Forest plot for AUC of p-tau 181 estimated from the individual studies and their respective weight. Legend: AUC: area under the receiver operating characteristic curve; CI: confidence interval; size: sample size (number); FU: follow-up (years). The solid line corresponds to an AUC of 0.73, a value considered acceptable for the ability of p-tau 181 to discriminate between MCI converters and non-converters. All studies [30,31,56,57,59,60,61,62,63,64,65] were beyond this line except for Park 2024 [66].
Figure 4
Figure 4
Bubble plot showing the logitAUC (effect size) of p-tau 181 estimated for the individual studies plotted (circle) against follow-up duration. Legend: FU: follow-up.
Figure 5
Figure 5
Bubble plot showing the logitAUC (effect size) of p-tau 181 estimated for the individual studies (circle) plotted against participants’ age (years).
Figure 6
Figure 6
Forest plot for AUC of p-tau 181 estimated from A+ studies (biologically confirmed ADD diagnosis) and from A− studies (only clinical ADD diagnosis). Legend: size: sample size (number). The solid vertical line set on the pooled AUC, 0.73. The AUC in the A+ studies (0.79) was superior to the AUC in the A− studies (0.71), but the difference was not statistically significant [30,31,56,57,59,60,61,62,63,64,65,66].
Figure 7
Figure 7
Forest plot for blood p-tau 217 of the SMD of the individual studies and their respective weight. A positive SMD indicates higher p-tau 217 values in participants who converted to ADD. Legend: size: sample size (number); FU: follow-up (years); the solid vertical line set on overall SMD results (1.49), [30,31,58].
Figure 8
Figure 8
Forest plot for AUC of p-tau 217 estimated from the individual studies and their respective weight. Legend: AUC: area under the receiver operating characteristic curve; CI: confidence interval; size: sample size (number); FU: follow-up (years). The solid vertical line is set on the pooled AUC for p-tau 217 (0.85), [30,31,58,59].
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