Blood amyloid and tau biomarkers as predictors of cerebrospinal fluid profiles

Delaby, Constance; Alcolea, Daniel; Hirtz, Christophe; Vialaret, Jérôme; Kindermans, Jana; Morichon, Lisa; Fortea, Juan; Gabelle, Audrey; Blennow, Kaj; Zetterberg, Henrik; Lleó, Alberto; Lehmann, Sylvain

doi:10.1007/s00702-022-02474-9

Cited by 13 publications

(8 citation statements)

References 25 publications

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“…The amyloid status, Aβ+ corresponding to the (A+) ATN classification,3 was defined based on the CSF Aβ1–42/Aβ1–40 ratio 23. Almost half of the MCI participants had a lumbar puncture and 117 of them were Aβ+ and 97 were Aβ−.…”

Section: Resultsmentioning

confidence: 99%

Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function

Lehmann

Schraen‐Maschke

Vidal

et al. 2023

J Neurol Neurosurg Psychiatry

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ObjectivesPlasma P-tau181 is an increasingly established diagnostic marker for Alzheimer’s disease (AD). Further validation in prospective cohorts is still needed, as well as the study of confounding factors that could influence its blood level.MethodsThis study is ancillary to the prospective multicentre Biomarker of AmyLoid pepTide and AlZheimer’s diseAse Risk cohort that enrolled participants with mild cognitive impairment (MCI) who were examined for conversion to dementia for up to 3 years. Plasma Ptau-181 was measured using the ultrasensitive Quanterix HD-X assay.ResultsAmong 476 MCI participants, 67% were amyloid positive (Aβ+) at baseline and 30% developed dementia. Plasma P-tau181 was higher in the Aβ+ population (3.9 (SD 1.4) vs 2.6 (SD 1.4) pg/mL) and in MCI that converted to dementia (3.8 (SD 1.5) vs 2.9 (SD 1.4) pg/mL). The addition of plasma P-tau181 to a logistic regression model combining age, sex, APOEε4 status and Mini Mental State Examination improved predictive performance (areas under the curve 0.691–0.744 for conversion and 0.786–0.849 for Aβ+). The Kaplan-Meier curve of conversion to dementia, according to the tertiles of plasma P-tau181, revealed a significant predictive value (Log rank p<0.0001) with an HR of 3.8 (95% CI 2.5 to 5.8). In addition, patients with plasma P-Tau(181) ≤2.32 pg/mL had a conversion rate of less than 20% over a 3-year period. Using a linear regression approach, chronic kidney disease, creatinine and estimated glomerular filtration rate were independently associated with plasma P-tau181 concentrations.ConclusionsPlasma P-tau181 effectively detects Aβ+ status and conversion to dementia, confirming the value of this blood biomarker for the management of AD. However, renal function significantly modifies its levels and may thus induce diagnostic errors if not taken into account.

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Section: Resultsmentioning

confidence: 99%

Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function

Lehmann

Schraen‐Maschke

Vidal

et al. 2023

J Neurol Neurosurg Psychiatry

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“…The amyloid status Aβ+ corresponding to the (A+) ATN classification 3 was defined based on the CSF Aβ1-42/Aβ1-40 ratio as previously reported 21 . Only part of MCI participants had a lumbar puncture and 117 of them were Aβ+ and 97 Aβ-.…”

Section: Comparison Between Aβ+ and Aβ-patientsmentioning

confidence: 99%

Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function

Lehmann

Schraen‐Maschke

Vidal

et al. 2022

Preprint

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BackgroundPlasma P-tau181 is associated with tau and amyloid pathology in Alzheimer’s disease (AD). Its use as a biomarker for the detection of AD (along the disease continuum, from preclinical to mild cognitive impairment (MCI) and dementia) is increasingly established, as is its prognostic value. Further validation in different settings of use is still needed, as well as investigation of confounding factors that might indirectly influence its blood concentration.MethodsThis study is ancillary to the prospective multicenter BALTAZAR cohort that enrolled patients with MCI according to Petersen criteria. Amyloid-positive (Aβ+) status was based on assessment of the cerebrospinal fluid (CSF) Aβ1-42/Aβ1-40 ratio, and participants were examined for conversion to dementia for up to three years. Plasma Ptau-181 was measured using an ultrasensitive assay and its diagnostic performance for Aβ+ and conversion to dementia were studied, as well as evaluation of the impact of comorbidities and biological confounders.FindingsAmong 476 MCI participants (mean MMSE score of 26·4 [SD 2·5] and 39·8% carrying APOE ε4), 67% were Aβ+ and 30% developed dementia (95% probable AD) at a mean of 14·6 [SD 8·2] months after the baseline. Independently of age, sex, and APOEε4, plasma P-tau181 was increased significantly by 30% between non-converters and converters (2·9 [SD 1·4] vs. 3·8 [SD 1·5] pg/mL, p<0·0001) and by 50% between Aβ- and Aβ+ (2·6 [SD 1·4] vs. 3·9 [SD 1·4] pg/mL, p<0·0001). Logistic regression was used to compare conversion and Aβ+ detection combining age, sex, APOEε4 status and MMSE without or with the addition of plasma P-tau181 which significantly improves performance (AUC 0·691 to 0·744 for conversion and 0·786 to 0·849 for Aβ+). CSF P-tau181 did not perform better in the same setting. Using a linear regression approach, chronic kidney disease (CKD), creatinine and glomerular filtration rate were independently associated with plasma P-tau181 concentrations, thereby altering the optimal cutpoints for Aβ+ or conversion to dementia detection.InterpretationPlasma P-tau181 effectively detects Aβ+ and conversion to dementia in a manner similar to CSF P-tau181, making this blood biomarker central to AD management. However, renal function significantly alters concentrations and will induce diagnostic error if not systematically taken into account.

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“…In this context, primary targets include biomarkers of Aβ pathology, tau pathology, neurodegeneration, and markers of glial reactivity. 10 Recent studies validated a high performance of plasma concentrations of Aβ40 and Aβ42, [11][12][13][14] phosphorylated tau (p-tau) 181, [14][15][16][17][18][19] p-tau231, 20 neurofilament light (NfL), 21 and glial fibrillary acidic protein (GFAP) 22,23 in confirming AD pathologies, axonal injury, and astrocytic activation. Some but not all of these biomarkers are increased in preclinical AD, 24,25 In recent years, intensified effort has, thus, been put into determining the influence of pre-analytical procedures, 26,27 storage stability, 28 and freeze-thaw cycles 29,30 on biomarker analysis to recommend a standardized procedure for sample handling and protein measurement.…”

Section: Introductionmentioning

confidence: 95%

“…In this context, primary targets include biomarkers of Aβ pathology, tau pathology, neurodegeneration, and markers of glial reactivity 10 . Recent studies validated a high performance of plasma concentrations of Aβ40 and Aβ42, 11–14 phosphorylated tau (p‐tau) 181, 14–19 p‐tau231, 20 neurofilament light (NfL), 21 and glial fibrillary acidic protein (GFAP) 22,23 in confirming AD pathologies, axonal injury, and astrocytic activation. Some but not all of these biomarkers are increased in preclinical AD, 24,25 and are associated with disease progression.…”

Section: Introductionmentioning

confidence: 99%

Levels of Alzheimer's disease blood biomarkers are altered after food intake—A pilot intervention study in healthy adults

Huber,

Ashton,

Schieren

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONBlood biomarkers accurately identify Alzheimer's disease (AD) pathophysiology and axonal injury. We investigated the influence of food intake on AD‐related biomarkers in cognitively healthy, obese adults at high metabolic risk.METHODSOne‐hundred eleven participants underwent repeated blood sampling during 3 h after a standardized meal (postprandial group, PG). For comparison, blood was sampled from a fasting subgroup over 3 h (fasting group, FG). Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), amyloid‐beta (Aβ) 42/40, phosphorylated tau (p‐tau) 181 and 231, and total‐tau were measured via single molecule array assays.RESULTSSignificant differences were found for NfL, GFAP, Aβ42/40, p‐tau181, and p‐tau231 between FG and PG. The greatest change to baseline occurred for GFAP and p‐tau181 (120 min postprandially, p < 0.0001).CONCLUSIONOur data suggest that AD‐related biomarkers are altered by food intake. Further studies are needed to verify whether blood biomarker sampling should be performed in the fasting state.Highlights Acute food intake alters plasma biomarkers of Alzheimer's disease in obese, otherwise healthy adults. We also found dynamic fluctuations in plasma biomarkers concentration in the fasting state suggesting physiological diurnal variations. Further investigations are highly needed to verify if biomarker measurements should be performed in the fasting state and at a standardized time of day to improve the diagnostic accuracy.

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Blood amyloid and tau biomarkers as predictors of cerebrospinal fluid profiles

Cited by 13 publications

References 25 publications

Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function

Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function

Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function

Levels of Alzheimer's disease blood biomarkers are altered after food intake—A pilot intervention study in healthy adults

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