Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease

Yara Yakoub; Nicholas J. Ashton; Cherie Strikwerda-Brown; Laia Montoliu-Gaya; Thomas K. Karikari; Przemysław R. Kac; Fernando Gonzalez-Ortiz; Jonathan Gallego-Rudolf; Pierre François Meyer; Frédéric St-Onge; Michael Schöll; Jean Paul Soucy; John C.S. Breitner; Henrik Zetterberg; Kaj Blennow; Judes Poirier; Sylvia Villeneuve

doi:10.1002/alz.13318

Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease

Yara Yakoub, Nicholas J. Ashton, Cherie Strikwerda-Brown, Laia Montoliu-Gaya, Thomas K. Karikari, Przemysław R. Kac, Fernando Gonzalez-Ortiz, Jonathan Gallego-Rudolf, Pierre François Meyer, Frédéric St-Onge, Michael Schöll, Jean Paul Soucy, John C.S. Breitner, Henrik Zetterberg, Kaj Blennow, Judes Poirier, Sylvia Villeneuve

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

INTRODUCTION: Plasma biomarkers are altered years prior to Alzheimer's disease (AD) clinical onset. METHODS: We measured longitudinal changes in plasma amyloid-beta (Aβ)_42/40 ratio, pTau181, pTau231, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in a cohort of older adults at risk of AD (n = 373 total, n = 229 with Aβ and tau positron emission tomography [PET] scans) considering genetic and demographic factors as possible modifiers of these markers’ progression. RESULTS: Aβ_42/40 ratio concentrations decreased, while NfL and GFAP values increased over the 4-year follow-up. Apolipoprotein E (APOE) ε4 carriers showed faster increase in plasma pTau181 than non-carriers. Older individuals showed a faster increase in plasma NfL, and females showed a faster increase in plasma GFAP values. In the PET subsample, individuals both Aβ-PET and tau-PET positive showed faster plasma pTau181 and GFAP increase compared to PET-negative individuals. DISCUSSION: Plasma markers can track biological change over time, with plasma pTau181 and GFAP markers showing longitudinal change in individuals with preclinical AD. Highlights: Longitudinal increase of plasma pTau181 and glial fibrillary acidic protein (GFAP) can be measured in the preclinical phase of AD. Apolipoprotein E ε4 carriers experience faster increase in plasma pTau181 over time than non-carriers. Female sex showed accelerated increase in plasma GFAP over time compared to males. Aβ_42/40 and pTau231 values are already abnormal at baseline in individuals with both amyloid and tau PET burden.

Original language	English
Pages (from-to)	5620-5631
Number of pages	12
Journal	Alzheimer's and Dementia
Volume	19
Issue number	12
DOIs	https://doi.org/10.1002/alz.13318
Publication status	Published - Dec 2023
Externally published	Yes

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Yakoub, Y., Ashton, N. J., Strikwerda-Brown, C., Montoliu-Gaya, L., Karikari, T. K., Kac, P. R., Gonzalez-Ortiz, F., Gallego-Rudolf, J., Meyer, P. F., St-Onge, F., Schöll, M., Soucy, J. P., Breitner, J. C. S., Zetterberg, H., Blennow, K., Poirier, J., & Villeneuve, S. (2023). Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease. Alzheimer's and Dementia, 19(12), 5620-5631. https://doi.org/10.1002/alz.13318

@article{bb392a388f4a4bf6a4671de011726c0f,

title = "Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease",

abstract = "INTRODUCTION: Plasma biomarkers are altered years prior to Alzheimer's disease (AD) clinical onset. METHODS: We measured longitudinal changes in plasma amyloid-beta (Aβ)42/40 ratio, pTau181, pTau231, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in a cohort of older adults at risk of AD (n = 373 total, n = 229 with Aβ and tau positron emission tomography [PET] scans) considering genetic and demographic factors as possible modifiers of these markers{\textquoteright} progression. RESULTS: Aβ42/40 ratio concentrations decreased, while NfL and GFAP values increased over the 4-year follow-up. Apolipoprotein E (APOE) ε4 carriers showed faster increase in plasma pTau181 than non-carriers. Older individuals showed a faster increase in plasma NfL, and females showed a faster increase in plasma GFAP values. In the PET subsample, individuals both Aβ-PET and tau-PET positive showed faster plasma pTau181 and GFAP increase compared to PET-negative individuals. DISCUSSION: Plasma markers can track biological change over time, with plasma pTau181 and GFAP markers showing longitudinal change in individuals with preclinical AD. Highlights: Longitudinal increase of plasma pTau181 and glial fibrillary acidic protein (GFAP) can be measured in the preclinical phase of AD. Apolipoprotein E ε4 carriers experience faster increase in plasma pTau181 over time than non-carriers. Female sex showed accelerated increase in plasma GFAP over time compared to males. Aβ42/40 and pTau231 values are already abnormal at baseline in individuals with both amyloid and tau PET burden.",

keywords = "Alzheimer's disease, Aβ, biomarker, PET, plasma, pTau",

author = "Yara Yakoub and Ashton, {Nicholas J.} and Cherie Strikwerda-Brown and Laia Montoliu-Gaya and Karikari, {Thomas K.} and Kac, {Przemys{\l}aw R.} and Fernando Gonzalez-Ortiz and Jonathan Gallego-Rudolf and Meyer, {Pierre Fran{\c c}ois} and Fr{\'e}d{\'e}ric St-Onge and Michael Sch{\"o}ll and Soucy, {Jean Paul} and Breitner, {John C.S.} and Henrik Zetterberg and Kaj Blennow and Judes Poirier and Sylvia Villeneuve",

year = "2023",

month = dec,

doi = "10.1002/alz.13318",

language = "English",

volume = "19",

pages = "5620--5631",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Academic Press",

number = "12",

}

Yakoub, Y, Ashton, NJ, Strikwerda-Brown, C, Montoliu-Gaya, L, Karikari, TK, Kac, PR, Gonzalez-Ortiz, F, Gallego-Rudolf, J, Meyer, PF, St-Onge, F, Schöll, M, Soucy, JP, Breitner, JCS, Zetterberg, H, Blennow, K, Poirier, J & Villeneuve, S 2023, 'Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease', Alzheimer's and Dementia, vol. 19, no. 12, pp. 5620-5631. https://doi.org/10.1002/alz.13318

TY - JOUR

T1 - Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease

AU - Yakoub, Yara

AU - Ashton, Nicholas J.

AU - Strikwerda-Brown, Cherie

AU - Montoliu-Gaya, Laia

AU - Karikari, Thomas K.

AU - Kac, Przemysław R.

AU - Gonzalez-Ortiz, Fernando

AU - Gallego-Rudolf, Jonathan

AU - Meyer, Pierre François

AU - St-Onge, Frédéric

AU - Schöll, Michael

AU - Soucy, Jean Paul

AU - Breitner, John C.S.

AU - Zetterberg, Henrik

AU - Blennow, Kaj

AU - Poirier, Judes

AU - Villeneuve, Sylvia

PY - 2023/12

Y1 - 2023/12

N2 - INTRODUCTION: Plasma biomarkers are altered years prior to Alzheimer's disease (AD) clinical onset. METHODS: We measured longitudinal changes in plasma amyloid-beta (Aβ)42/40 ratio, pTau181, pTau231, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in a cohort of older adults at risk of AD (n = 373 total, n = 229 with Aβ and tau positron emission tomography [PET] scans) considering genetic and demographic factors as possible modifiers of these markers’ progression. RESULTS: Aβ42/40 ratio concentrations decreased, while NfL and GFAP values increased over the 4-year follow-up. Apolipoprotein E (APOE) ε4 carriers showed faster increase in plasma pTau181 than non-carriers. Older individuals showed a faster increase in plasma NfL, and females showed a faster increase in plasma GFAP values. In the PET subsample, individuals both Aβ-PET and tau-PET positive showed faster plasma pTau181 and GFAP increase compared to PET-negative individuals. DISCUSSION: Plasma markers can track biological change over time, with plasma pTau181 and GFAP markers showing longitudinal change in individuals with preclinical AD. Highlights: Longitudinal increase of plasma pTau181 and glial fibrillary acidic protein (GFAP) can be measured in the preclinical phase of AD. Apolipoprotein E ε4 carriers experience faster increase in plasma pTau181 over time than non-carriers. Female sex showed accelerated increase in plasma GFAP over time compared to males. Aβ42/40 and pTau231 values are already abnormal at baseline in individuals with both amyloid and tau PET burden.

AB - INTRODUCTION: Plasma biomarkers are altered years prior to Alzheimer's disease (AD) clinical onset. METHODS: We measured longitudinal changes in plasma amyloid-beta (Aβ)42/40 ratio, pTau181, pTau231, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in a cohort of older adults at risk of AD (n = 373 total, n = 229 with Aβ and tau positron emission tomography [PET] scans) considering genetic and demographic factors as possible modifiers of these markers’ progression. RESULTS: Aβ42/40 ratio concentrations decreased, while NfL and GFAP values increased over the 4-year follow-up. Apolipoprotein E (APOE) ε4 carriers showed faster increase in plasma pTau181 than non-carriers. Older individuals showed a faster increase in plasma NfL, and females showed a faster increase in plasma GFAP values. In the PET subsample, individuals both Aβ-PET and tau-PET positive showed faster plasma pTau181 and GFAP increase compared to PET-negative individuals. DISCUSSION: Plasma markers can track biological change over time, with plasma pTau181 and GFAP markers showing longitudinal change in individuals with preclinical AD. Highlights: Longitudinal increase of plasma pTau181 and glial fibrillary acidic protein (GFAP) can be measured in the preclinical phase of AD. Apolipoprotein E ε4 carriers experience faster increase in plasma pTau181 over time than non-carriers. Female sex showed accelerated increase in plasma GFAP over time compared to males. Aβ42/40 and pTau231 values are already abnormal at baseline in individuals with both amyloid and tau PET burden.

KW - Alzheimer's disease

KW - Aβ

KW - biomarker

KW - PET

KW - plasma

KW - pTau

UR - http://www.scopus.com/inward/record.url?scp=85163068783&partnerID=8YFLogxK

U2 - 10.1002/alz.13318

DO - 10.1002/alz.13318

M3 - Article

C2 - 37294682

AN - SCOPUS:85163068783

SN - 1552-5260

VL - 19

SP - 5620

EP - 5631

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 12

ER -

Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease

Abstract

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