Plasma Aβ42/Aβ40 and p-tau181 Predict Long-Term Clinical Progression in a Cohort with Amnestic Mild Cognitive Impairment

Abstract

Background Previous studies reported the value of blood-based biomarkers in predicting Alzheimer disease (AD) progression among individuals with different disease stages. However, evidence regarding the value of these markers in those with amnestic mild cognitive impairment (aMCI) is insufficient. Methods A cohort with 251 aMCI individuals were followed for up to 8 years. Baseline blood biomarkers were measured on a single-molecule array platform. Multipoint clinical diagnosis and domain-specific cognitive functions were assessed to investigate the longitudinal relationship between blood biomarkers and clinical AD progression. Results Individuals with low Aβ42/Aβ40 and high p-tau181 at baseline demonstrated the highest AD risk (hazard ratio = 4.83, 95% CI 2.37–9.86), and the most dramatic decline across cognitive domains. Aβ42/Aβ40 and p-tau181, combined with basic characteristics performed the best in predicting AD conversion (AUC = 0.825, 95% CI 0.771–0.878). Conclusions Combining Aβ42/Aβ40 and p-tau181 may be a feasible indicator for AD progression in clinical practice, and a potential composite marker in clinical trials.

Risk of cognitive decline progression is associated to increased blood‐brain‐barrier permeability: A longitudinal study in a memory unit clinical cohort

“…Multiple studies have analyzed possible predictors that identify subjects at higher risk of clinical worsening, most of them in the AD continuum assessing AD pathology‐related fluid biomarkers as well as imaging biomarkers such as the dementia conversion‐related pattern (ADCRP) on [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG PET) 43–47 . Our results show factors already described as strongly associated with progression of cognitive decline such as b‐AD (abnormal Aβ42/p‐Tau181 ratio), APOE‐ε4 carrier status, and female sex 48 .…”

The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study

“…Plasma phosphorylated tau including P-tau181, P-tau217, and P-tau231 had been validated as a promising marker for AD [ 7 , 34 , 49 ]. Plasma P-tau181 showed great potential in AD diagnosis [ 2 ], cognitive outcome prediction [ 21 ], and amyloid and tau PET staging [ 50 ].…”

“…Alzheimer’s disease (AD) is the leading cause of dementia [ 1 ]. Recently, blood-based biomarkers have been established as a non-invasive and cost-effective measure in AD, for early diagnosis [ 2 ], differential diagnosis [ 3 ], outcome prediction [ 4 , 5 ], and longitudinal disease monitoring [ 6 , 7 ]. Plasma neurofilament light chain (NfL) and phospho-tau181 (P-tau181) are promising AD biomarkers.…”

Association of plasma biomarkers of Alzheimer's disease and related disorders with cognition and cognitive decline: The MYHAT population‐based study

“… 3 , 4 , 5 Amyloid beta 42/40 (Aβ42/40) ratio, phosphorylated tau at threonine‐181 (p‐tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) are among the most extensively studied blood biomarkers of ADRD. 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 Recent studies have shown strong correlations of plasma Aβ42/40 ratio and p‐tau181 with brain Aβ burden, as well as with concurrent and subsequent cognitive performance. 6 , 16 , 17 , 18 , 19 , 20 , 21 , 22 Plasma p‐tau181 shows good correlations with brain tau burden, while plasma NfL associates with magnetic resonance imaging (MRI)‐ and CSF‐assessed neurodegeneration in AD and ADRD.…”