Alzheimer's & dementia (Amsterdam, Netherlands) · 2026
Copper isotope shifts in biofluids track Alzheimer's pathology.
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Lahoud Esther, Moynier Frédéric, Mahan Brandon, Luu Tu-Han, Rigoussen Dimitri, Le Borgne Marie, Paquet Claire, Fowler Christopher, Bush Ashley I
Аннотация
INTRODUCTION: Altered copper metabolism has been reported in Alzheimer's disease (AD), with post mortem brain tissue showing depletion of 65Cu compared with 63Cu. Whether such isotopic shifts can be detected in biofluids remains unknown.
METHODS: We analyzed copper isotope composition in human cerebrospinal fluid (CSF) and serum from AD patients and controls using multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) and single quadrupole inductively coupled plasma mass spectrometry (SQ-ICP-MS). Samples included 22 CSFs (10 AD, 12 controls), 54 sera (28 AD, 26 controls).
RESULTS: AD CSF was enriched in 65Cu (+0.32‰, p = 0.02), correlating inversely with CSF amyloid beta (Aβ)42/40 ratios. Serum from AD patients was depleted in 65Cu (-0.23‰, p = 0.013), trending inversely with amyloid positron emission tomography burden. Serum and CSF δ 65Cu diagnostically discriminate between AD and controls (area under the curve = 0.8, Youden's J ≈ 0.5 SD, p ≤ 0.0002).
DISCUSSION: Copper isotope excursions in brain parenchyma are mirrored in CSF and serum. These shifts reflect amyloid pathology and highlight isotopic copper analysis as a potential minimally invasive biomarker for AD.
METHODS: We analyzed copper isotope composition in human cerebrospinal fluid (CSF) and serum from AD patients and controls using multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) and single quadrupole inductively coupled plasma mass spectrometry (SQ-ICP-MS). Samples included 22 CSFs (10 AD, 12 controls), 54 sera (28 AD, 26 controls).
RESULTS: AD CSF was enriched in 65Cu (+0.32‰, p = 0.02), correlating inversely with CSF amyloid beta (Aβ)42/40 ratios. Serum from AD patients was depleted in 65Cu (-0.23‰, p = 0.013), trending inversely with amyloid positron emission tomography burden. Serum and CSF δ 65Cu diagnostically discriminate between AD and controls (area under the curve = 0.8, Youden's J ≈ 0.5 SD, p ≤ 0.0002).
DISCUSSION: Copper isotope excursions in brain parenchyma are mirrored in CSF and serum. These shifts reflect amyloid pathology and highlight isotopic copper analysis as a potential minimally invasive biomarker for AD.