Dataset Information

The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease.

ABSTRACT:

Introduction

This study investigated the diagnostic and disease-monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals.

Methods

Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants.

Results

Phosphorylated-tau181 (P-tau181), neurofilament light, amyloid-β (Aβ42/40), Total-tau and Glial fibrillary acidic protein were altered in AD dementia but P-tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P-tau181 was increased in MCI converters compared to non-converters. Higher P-tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P-tau181 was strongly associated with gray matter loss in the full sample and with Aβ measures in CU individuals.

Discussion

P-tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P-tau181 as a non-invasive and cost-effective diagnostic and prognostic biomarker in AD.

SUBMITTER: Simren J

PROVIDER: S-EPMC8359457 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease.

Simrén Joel J Leuzy Antoine A Karikari Thomas K TK Hye Abdul A Benedet Andréa Lessa AL Lantero-Rodriguez Juan J Mattsson-Carlgren Niklas N Schöll Michael M Mecocci Patrizia P Vellas Bruno B Tsolaki Magda M Kloszewska Iwona I Soininen Hilkka H Lovestone Simon S Aarsland Dag D Hansson Oskar O Rosa-Neto Pedro P Westman Eric E Blennow Kaj K Zetterberg Henrik H Ashton Nicholas J NJ

Alzheimer's & dementia : the journal of the Alzheimer's Association 20210125 7

<h4>Introduction</h4>This study investigated the diagnostic and disease-monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals.<h4>Methods</h4>Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants.<h4>Results</h4>Phosphorylated-tau181 (P-tau181), neurofilament light, amyloid-β (Aβ42/40), Total-tau and Glial fibrillary acidic protein were altered in AD dem ...[more]

PMID: 33491853

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Project description:BackgroundBlood-based biomarkers offer a promising, less invasive, and more cost-effective alternative for Alzheimer's disease screening compared to cerebrospinal fluid or imaging biomarkers. However, they have been extensively studied only in memory clinic-based cohorts. We aimed to validate them in a more heterogeneous, older patient population from primary care.MethodsWe measured plasma Aβ42/Aβ40, P-tau181, NfL, and GFAP in 1007 individuals without dementia, aged 79-94 years, from the longitudinal, primary care-based German AgeCoDe study. We assessed the association with cognitive decline, disease progression, and the capacity to predict future dementia of the Alzheimer's type (DAT). We also evaluated biomarker dynamics in 305 individuals with a follow-up sample (∼8 years later).FindingsHigher levels of P-tau181 (HR = 1.32 [95% CI: 1.17-1.51]), NfL (HR = 1.19 [95% CI: 1.03-1.36]), and GFAP (HR = 1.36 [95% CI: 1.22-1.52]), and a lower Aβ42/Aβ40 ratio (HR = 0.80 [95% CI: 0.68-0.95]) were associated with an increased risk of progressing to clinically-diagnosed DAT. Additionally, higher levels of P-tau181 (β = -0.49 [95% CI: -0.71 to 0.26]), NfL (β = -0.29 [95% CI: -0.52 to 0.06]), and GFAP (β = -0.60 [95% CI: -0.83 to 0.38]) were linked to faster cognitive decline. A two-step DAT prediction strategy combining initial MMSE with biomarkers improved the identification of individuals in the prodromal stage for potential treatment eligibility. Biomarker levels changed over time, with increases in P-tau181 (β = 0.19 [95% CI: 0.14-0.25]), NfL (β = 2.88 [95% CI: 2.18-3.59]), and GFAP (β = 8.23 [95% CI: 6.71-9.75]). NfL (β = 2.47 [95% CI: 1.04-3.89]) and GFAP (β = 4.45 [95% CI: 1.38-7.51]) exhibited a faster increase in individuals progressing to DAT.InterpretationEvaluating plasma biomarkers, alongside brief cognitive assessments, might enhance the precision of risk assessment for DAT progression in primary care.FundingAlzheimer Forschung Initiative, Bundesministerium für Bildung und Forschung.

Dataset Information

The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease.

Introduction

Methods

Results

Discussion

Publications

The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease.

Similar Datasets

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