Copper isotope shifts in biofluids track Alzheimer's pathology
Abstract
INTRODUCTION Altered copper metabolism has been reported in Alzheimer's disease (AD), with post mortem brain tissue showing depletion of 65 Cu compared with 63 Cu. 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 65 Cu (+0.32‰, p = 0.02), correlating inversely with CSF amyloid beta (Aβ) 42/40 ratios. Serum from AD patients was depleted in 65 Cu (−0.23‰, p = 0.013), trending inversely with amyloid positron emission tomography burden. Serum and CSF δ 65 Cu 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.
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BibTeX
@article{lahoud2026copper,
title = {{Copper isotope shifts in biofluids track Alzheimer's pathology}},
author = {Esther Lahoud and Frédéric Moynier and Brandon Mahan and Tu‐han Luu and Dimitri Rigoussen and Marie Le Borgne and Claire Paquet and Christopher Fowler and Ashley Bush},
journal = {Alzheimer's \& Dementia: Diagnosis, Assessment \& Disease Monitoring},
year = {2026},
month = jun,
doi = {10.1002/dad2.70316},
url = {https://hal.science/hal-05774438v1},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Copper isotope shifts in biofluids track Alzheimer's pathology
AU - Esther Lahoud
AU - Frédéric Moynier
AU - Brandon Mahan
AU - Tu‐han Luu
AU - Dimitri Rigoussen
AU - Marie Le Borgne
AU - Claire Paquet
AU - Christopher Fowler
AU - Ashley Bush
PY - 2026
DA - 2026/06/15
JO - Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
DO - 10.1002/dad2.70316
UR - https://hal.science/hal-05774438v1
AB - INTRODUCTION Altered copper metabolism has been reported in Alzheimer's disease (AD), with post mortem brain tissue showing depletion of 65 Cu compared with 63 Cu. 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 65 Cu (+0.32‰, p = 0.02), correlating inversely with CSF amyloid beta (Aβ) 42/40 ratios. Serum from AD patients was depleted in 65 Cu (−0.23‰, p = 0.013), trending inversely with amyloid positron emission tomography burden. Serum and CSF δ 65 Cu 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.
SN - 2352-8729
ER -