Brain Aβ load association and sexual dimorphism of plasma BACE1 concentrations in cognitively normal individuals at risk for AD

the INSIGHT-preAD study group, Alzheimer Precision Medicine Initiative (APMI)

Research output: Contribution to journalArticle

Abstract

Introduction: Successful development of effective β-site amyloid precursor protein cleaving enzyme 1 (BACE1)–targeted therapies for early stages of Alzheimer's disease requires biomarker-guided intervention strategies. Methods: We investigated whether key biological factors such as sex, apolipoprotein E (APOE ε4) allele, and age affect longitudinal plasma BACE1 concentrations in a large monocenter cohort of individuals at risk for Alzheimer's disease. We explored the relationship between plasma BACE1 concentrations and levels of brain amyloid-β (Aβ) deposition, using positron emission tomography global standard uptake value ratios. Results: Baseline and longitudinal mean concentrations of plasma BACE1 were significantly higher in women than men. We also found a positive significant impact of plasma BACE1 on baseline Aβ–positron emission tomography global standard uptake value ratios. Discussion: Our results suggest a sexual dimorphism in BACE1-related upstream mechanisms of brain Aβ production and deposition. We argue that plasma BACE1 should be considered in further biomarker validation and qualification studies as well as in BACE1 clinical trials.

Original languageEnglish
Pages (from-to)1274-1285
Number of pages12
JournalAlzheimer's and Dementia
Volume15
Issue number10
DOIs
StatePublished - Oct 2019

Fingerprint

Sex Characteristics
Brain
Alzheimer Disease
Biomarkers
Apolipoprotein E4
Amyloid beta-Protein Precursor
Validation Studies
Biological Factors
Amyloid
Positron-Emission Tomography
Alleles
Tomography
Clinical Trials
Enzymes
Therapeutics

Keywords

  • Alzheimer's disease
  • BACE1 biomarkers
  • Disease modifying
  • Plasma BACE1
  • Sexual dimorphism

Cite this

the INSIGHT-preAD study group ; Alzheimer Precision Medicine Initiative (APMI). / Brain Aβ load association and sexual dimorphism of plasma BACE1 concentrations in cognitively normal individuals at risk for AD. In: Alzheimer's and Dementia. 2019 ; Vol. 15, No. 10. pp. 1274-1285.
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abstract = "Introduction: Successful development of effective β-site amyloid precursor protein cleaving enzyme 1 (BACE1)–targeted therapies for early stages of Alzheimer's disease requires biomarker-guided intervention strategies. Methods: We investigated whether key biological factors such as sex, apolipoprotein E (APOE ε4) allele, and age affect longitudinal plasma BACE1 concentrations in a large monocenter cohort of individuals at risk for Alzheimer's disease. We explored the relationship between plasma BACE1 concentrations and levels of brain amyloid-β (Aβ) deposition, using positron emission tomography global standard uptake value ratios. Results: Baseline and longitudinal mean concentrations of plasma BACE1 were significantly higher in women than men. We also found a positive significant impact of plasma BACE1 on baseline Aβ–positron emission tomography global standard uptake value ratios. Discussion: Our results suggest a sexual dimorphism in BACE1-related upstream mechanisms of brain Aβ production and deposition. We argue that plasma BACE1 should be considered in further biomarker validation and qualification studies as well as in BACE1 clinical trials.",
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author = "{the INSIGHT-preAD study group} and {Alzheimer Precision Medicine Initiative (APMI)} and Andrea Vergallo and Marion Houot and Enrica Cavedo and Pablo Lemercier and Eugeen Vanmechelen and {De Vos}, Ann and Habert, {Marie Odile} and Potier, {Marie Claude} and Bruno Dubois and Simone Lista and Harald Hampel and H. Bakardjian and H. Benali and H. Bertin and J. Bonheur and L. Boukadida and N. Boukerrou and E. Cavedo and P. Chiesa and O. Colliot and B. Dubois and M. Dubois and S. Epelbaum and G. Gagliardi and R. Genthon and Habert, {M. O.} and H. Hampel and M. Houot and A. Kas and F. Lamari and M. Levy and S. Lista and C. Metzinger and F. Mochel and F. Nyasse and C. Poisson and Potier, {M. C.} and M. Revillon and A. Santos and Andrade, {K. S.} and M. Sole and M. Surtee and {Thiebaud de Schotten}, M. and A. Vergallo and N. Younsi and Mohammad Afshar and {Flores Aguilar}, Lisi and Leyla Akman-Anderson and Joaqu{\'i}n Arenas and Jesus Avila",
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Brain Aβ load association and sexual dimorphism of plasma BACE1 concentrations in cognitively normal individuals at risk for AD. / the INSIGHT-preAD study group; Alzheimer Precision Medicine Initiative (APMI).

In: Alzheimer's and Dementia, Vol. 15, No. 10, 10.2019, p. 1274-1285.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Brain Aβ load association and sexual dimorphism of plasma BACE1 concentrations in cognitively normal individuals at risk for AD

AU - the INSIGHT-preAD study group

AU - Alzheimer Precision Medicine Initiative (APMI)

AU - Vergallo, Andrea

AU - Houot, Marion

AU - Cavedo, Enrica

AU - Lemercier, Pablo

AU - Vanmechelen, Eugeen

AU - De Vos, Ann

AU - Habert, Marie Odile

AU - Potier, Marie Claude

AU - Dubois, Bruno

AU - Lista, Simone

AU - Hampel, Harald

AU - Bakardjian, H.

AU - Benali, H.

AU - Bertin, H.

AU - Bonheur, J.

AU - Boukadida, L.

AU - Boukerrou, N.

AU - Cavedo, E.

AU - Chiesa, P.

AU - Colliot, O.

AU - Dubois, B.

AU - Dubois, M.

AU - Epelbaum, S.

AU - Gagliardi, G.

AU - Genthon, R.

AU - Habert, M. O.

AU - Hampel, H.

AU - Houot, M.

AU - Kas, A.

AU - Lamari, F.

AU - Levy, M.

AU - Lista, S.

AU - Metzinger, C.

AU - Mochel, F.

AU - Nyasse, F.

AU - Poisson, C.

AU - Potier, M. C.

AU - Revillon, M.

AU - Santos, A.

AU - Andrade, K. S.

AU - Sole, M.

AU - Surtee, M.

AU - Thiebaud de Schotten, M.

AU - Vergallo, A.

AU - Younsi, N.

AU - Afshar, Mohammad

AU - Flores Aguilar, Lisi

AU - Akman-Anderson, Leyla

AU - Arenas, Joaquín

AU - Avila, Jesus

PY - 2019/10

Y1 - 2019/10

N2 - Introduction: Successful development of effective β-site amyloid precursor protein cleaving enzyme 1 (BACE1)–targeted therapies for early stages of Alzheimer's disease requires biomarker-guided intervention strategies. Methods: We investigated whether key biological factors such as sex, apolipoprotein E (APOE ε4) allele, and age affect longitudinal plasma BACE1 concentrations in a large monocenter cohort of individuals at risk for Alzheimer's disease. We explored the relationship between plasma BACE1 concentrations and levels of brain amyloid-β (Aβ) deposition, using positron emission tomography global standard uptake value ratios. Results: Baseline and longitudinal mean concentrations of plasma BACE1 were significantly higher in women than men. We also found a positive significant impact of plasma BACE1 on baseline Aβ–positron emission tomography global standard uptake value ratios. Discussion: Our results suggest a sexual dimorphism in BACE1-related upstream mechanisms of brain Aβ production and deposition. We argue that plasma BACE1 should be considered in further biomarker validation and qualification studies as well as in BACE1 clinical trials.

AB - Introduction: Successful development of effective β-site amyloid precursor protein cleaving enzyme 1 (BACE1)–targeted therapies for early stages of Alzheimer's disease requires biomarker-guided intervention strategies. Methods: We investigated whether key biological factors such as sex, apolipoprotein E (APOE ε4) allele, and age affect longitudinal plasma BACE1 concentrations in a large monocenter cohort of individuals at risk for Alzheimer's disease. We explored the relationship between plasma BACE1 concentrations and levels of brain amyloid-β (Aβ) deposition, using positron emission tomography global standard uptake value ratios. Results: Baseline and longitudinal mean concentrations of plasma BACE1 were significantly higher in women than men. We also found a positive significant impact of plasma BACE1 on baseline Aβ–positron emission tomography global standard uptake value ratios. Discussion: Our results suggest a sexual dimorphism in BACE1-related upstream mechanisms of brain Aβ production and deposition. We argue that plasma BACE1 should be considered in further biomarker validation and qualification studies as well as in BACE1 clinical trials.

KW - Alzheimer's disease

KW - BACE1 biomarkers

KW - Disease modifying

KW - Plasma BACE1

KW - Sexual dimorphism

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