Plasma P-tau217 a Predictor for Cognitive Decline Among Patients With Preclinical AD

Plasma P-tau217 levels predicted cognitive decline in preclinical Alzheimer disease.

Cognitive decline in preclinical Alzheimer disease (AD) was predicted by plasma P-tau217 levels, according to results of a prospective population-based study, the results of which were published in JAMA Neurology.

Investigators from Lund University in Sweden sourced data for this study from the Swedish BioFINDER-1 and the Wisconsin Registry for Alzheimer Prevention (WRAP) cohorts which recruited cognitive unimpaired individuals with preclinical AD between 2010 and 2021. In this study, the change in plasma and cerebrospinal fluid (CSF) markers and positron emission tomography (PET) status were evaluated as markers for cognitive decline. Data from the WRAP study was used as the validation cohort. Cognition was assessed using the Mini-Mental State Examination (MMSE) and modified Alzheimer Cognitive Composite (mPACC) instruments.

In the BioFINDER-1 study, 286 participants were brain β-amyloid (Aβ)-negative and 119 were Aβ-positive and in WRAP, 107 were Aβ-negative and 52 Aβ-positive. The study cohorts comprised individuals aged mean 62.0-73.0 years, 34.6%-39.5% were men, 18.5%-65.4% were positive for apolipoprotein E4 (APOE4), mean MMSE score at baseline was 28.5-29.5 points, and mPACC was -0.79 to -0.07 points.

Using the BioFINDER-1 data, the change in MMSE scores over time associated with plasma P-tau217 (R2, 0.34; P <.001), plasma P-tau181 (R2, 0.24; P <.001), CSF P-tau2017 (R2, 0.24; P <.001), CSF P-tau181 (R2, 0.17; P <.001), CSF neurofilament light (NFL; R2, 0.15; P <.001), CSF Aβ42/40 (R2, 0.14; P <.001), plasma glial fibrillary filament protein (GFAP; R2, 0.13; P =.004), plasma NFL (R2, 0.12; P =.01), and CSF GFAP (R2, 0.09; P =.007) levels. The change in mPACC score over time associated with plasma P-tau217 (R2, 0.41; P <.001), CSF P-tau217 (R2, 0.37; P <.001), plasma P-tau181 (R2, 0.36; P <.001), plasma GFAP (R2, 0.30; P =.001), CSF Aβ42/40 (R2, 0.27; P =.01), and CSF P-tau181 (R2, 0.26; P =.02) levels.

These findings suggest that plasma P-tau217 may be used as a complement to CSF or PET for participant selection in clinical trials of novel disease-modifying treatments.

The model which was the best predictor for MMSE slopes (corrected Akaike information criterion [AIC], 311.98) included plasma P-tau217 (β, -0.400; P <.001) and CSF Aβ42/40 (β, 0.090; P =.13) and for mPACC slopes (corrected AIC, 15.00), included plasma P-tau217 (β, -0.098; P <.001), APOE4 status (β, 0.110; P =.03), gender (β, 0.090; P =.08), and mPACC at baseline (β, 0.078; P <.001).

In the BioFINDER-1 cohort, 118 Aβ-positive individuals were evaluated for conversion to AD dementia and 30.5% were found to have converted. Plasma P-tau217 at baseline associated with a risk for conversion to AD dementia (hazard ratio [HR], 2.03; 95% CI, 1.57-2.63; P <.001).

In the WRAP cohort, plasma P-tau217 (R2, 0.13; P =.01) and amyloid PET (R2, 0.10; P =.02) data improved the fit of a covariates-only model for predicting mPACC slopes. For MMSE slopes, plasma P-tau217 improved the model fit (R2, 0.29; P =.046), but amyloid PET did not (R2, 0.28; P =.07).

The major limitation of this study was the lack of CSF and PET evaluations in both cohorts.

Study authors concluded, “This prognostic study found that plasma P-tau217 predicted cognitive decline in individuals with preclinical AD. These findings suggest that plasma P-tau217 may be used as a complement to CSF or PET for participant selection in clinical trials of novel disease-modifying treatments.”

Disclosure: Multiple authors declared industry affiliations. Please refer to the original article for a full list of disclosures.     

References:

Mattsson-Carlgren N, Salvadó G, Ashton NJ, et al. Prediction of longitudinal cognitive decline in preclinical Alzheimer disease using plasma biomarkers. JAMA Neurol. Published online Febrary 6, 2023. doi:10.1001/jamaneurol.2022.5272