Andrea Vergallo1, Pablo Lemercier1, Enrica Cavedo1, Simone Lista1, Eugeen Vanmechelen2, Ann De Vos2, Henrik Zetterberg3,4,5,6, Kaj Blennow4,5, Marie-Odile Habert7,8,9, Marie-Claude Potier10, Bruno Dubois1, Stefan Teipel11,12, Harald Hampel1. 1. Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France. 2. ADx NeuroSciences NV2, Ghent, Belgium. 3. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 4. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 5. Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK. 6. UK Dementia Research Institute at UCL, London, UK. 7. Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, F-75013, Paris, France. 8. Centre pour l'Acquisition et le Traitement des Images, Paris, France. 9. AP-HP, Hôpital Pitié-Salpêtrière, Département de Médecine Nucléaire, Paris, France. 10. ICM Institut du Cerveau et de la Moelle épinière, CNRS UMR7225, INSERM U1127, UPMC, Hôpital de la Pitié-Salpêtrière, 47 Bd de l'Hôpital, Paris, France. 11. Clinical Dementia Research Section, German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany. 12. Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany.
Abstract
BACKGROUND: Increased β-secretase 1 (BACE1) protein concentration, in body fluids, is a candidate biomarker of Alzheimer's disease (AD).We reported that plasma BACE1 protein concentrations are associated with the levels of brain amyloidβ (Αβ) accumulation in cognitively healthy individuals with subjective memory complaint (SMC). METHODS: In 302 individuals from the same cohort, we investigated the cross-sectional and longitudinal association between plasma BACE1 protein concentrations and AD biomarkers of neurodegeneration (plasma t-tau and Neurofilament light chain (NfL), fluorodeoxyglucose-positron emission tomography (FDG-PET), brain volumes in the basal forebrain [BF], hippocampus, and entorhinal cortex). RESULTS: We report a positive longitudinal correlation of BACE1 with both NfL and t-tau, as well as a correlation between annual BACE1 changes and bi-annual reduction of BF volume. We show a positive association between BACE1 and FDG-PET signal at baseline. CONCLUSIONS: The association between plasma BACE1 protein concentrations and BF atrophy we found in cognitively healthy individuals with SMC corroborates translational studies, suggesting a role of BACE1 in neurodegeneration.
BACKGROUND: Increased β-secretase 1 (BACE1) protein concentration, in body fluids, is a candidate biomarker of Alzheimer's disease (AD).We reported that plasma BACE1 protein concentrations are associated with the levels of brain amyloidβ (Αβ) accumulation in cognitively healthy individuals with subjective memory complaint (SMC). METHODS: In 302 individuals from the same cohort, we investigated the cross-sectional and longitudinal association between plasma BACE1 protein concentrations and AD biomarkers of neurodegeneration (plasma t-tau and Neurofilament light chain (NfL), fluorodeoxyglucose-positron emission tomography (FDG-PET), brain volumes in the basal forebrain [BF], hippocampus, and entorhinal cortex). RESULTS: We report a positive longitudinal correlation of BACE1 with both NfL and t-tau, as well as a correlation between annual BACE1 changes and bi-annual reduction of BF volume. We show a positive association between BACE1 and FDG-PET signal at baseline. CONCLUSIONS: The association between plasma BACE1 protein concentrations and BF atrophy we found in cognitively healthy individuals with SMC corroborates translational studies, suggesting a role of BACE1 in neurodegeneration.