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 language | English |
|---|---|
| Pages (from-to) | 1274-1285 |
| Number of pages | 12 |
| Journal | Alzheimer's and Dementia |
| Volume | 15 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2019 |
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Keywords
- Alzheimer's disease
- BACE1 biomarkers
- Disease modifying
- Plasma BACE1
- Sexual dimorphism
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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 journal › Article
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
UR - http://www.scopus.com/inward/record.url?scp=85072861170&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2019.07.001
DO - 10.1016/j.jalz.2019.07.001
M3 - Article
C2 - 31627825
AN - SCOPUS:85072861170
VL - 15
SP - 1274
EP - 1285
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 10
ER -