Plasma β-secretase1 concentrations correlate with basal forebrain atrophy and neurodegeneration in cognitively healthy individuals at risk for AD.
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.
['Vergallo|Andrea|A|', 'Lemercier|Pablo|P|', 'Cavedo|Enrica|E|', 'Lista|Simone|S|', 'Vanmechelen|Eugeen|E|', 'De Vos|Ann|A|', 'Zetterberg|Henrik|H|', 'Blennow|Kaj|K|', 'Habert|Marie-Odile|MO|', 'Potier|Marie-Claude|MC|', 'Dubois|Bruno|B|', 'Teipel|Stefan|S|', 'Hampel|Harald|H|', '|||']
D000368:Aged D053829:Amyloid Precursor Protein Secretases D016229:Amyloid beta-Peptides D016282:Aspartic Acid Endopeptidases D001284:Atrophy D066187:Basal Forebrain D015415:Biomarkers D003430:Cross-Sectional Studies D005260:Female D005602:France D064368:Healthy Volunteers D006801:Humans D008297:Male D008569:Memory Disorders
basal forebrain neurodegeneration BACE1 Alzheimer's disease axonal damage preclinical