TY - JOUR
T1 - Multi-peptide characterization of plasma neurofilament light chain in preclinical and mild Alzheimer's disease
AU - Coulton, John B.
AU - He, Yingxin
AU - Barthélemy, Nicolas R.
AU - Jiang, Hong
AU - Holtzman, David M.
AU - Bateman, Randall J.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024
Y1 - 2024
N2 - Although neurofilament light chain is a well-known marker of neuronal damage, its characterization at the proteoform level is underdeveloped. Here, we describe a new method to profile and quantify neurofilament light chain in plasma at the peptide level, using three in-house monoclonal antibodies targeting distinct protein domains and nano-liquid chromatography coupled to high-resolution tandem mass spectrometry. This study profiled and compared plasma neurofilament light chain to CSF in 102 older individuals (73.9 ± 6.3 years old), 37 of which had a clinical dementia rating greater than 0. We observed elevated neurofilament light chain in preclinical Alzheimer's disease plasma for two measures (NfL101 and NfL324) and CSF for seven measures (NfL92, NfL101, NfL117, NfL137, NfL148, NfL165 and NfL530). We found five plasma peptides (NfL92, NfL101, NfL117, NfL324 and NfL530) significantly associated with age and two (NfL148 and NfL324) with body mass index.
AB - Although neurofilament light chain is a well-known marker of neuronal damage, its characterization at the proteoform level is underdeveloped. Here, we describe a new method to profile and quantify neurofilament light chain in plasma at the peptide level, using three in-house monoclonal antibodies targeting distinct protein domains and nano-liquid chromatography coupled to high-resolution tandem mass spectrometry. This study profiled and compared plasma neurofilament light chain to CSF in 102 older individuals (73.9 ± 6.3 years old), 37 of which had a clinical dementia rating greater than 0. We observed elevated neurofilament light chain in preclinical Alzheimer's disease plasma for two measures (NfL101 and NfL324) and CSF for seven measures (NfL92, NfL101, NfL117, NfL137, NfL148, NfL165 and NfL530). We found five plasma peptides (NfL92, NfL101, NfL117, NfL324 and NfL530) significantly associated with age and two (NfL148 and NfL324) with body mass index.
KW - biomarkers
KW - immunoprecipitation
KW - mass spectrometry
KW - neurodegeneration
KW - neurofilament
UR - http://www.scopus.com/inward/record.url?scp=85201903585&partnerID=8YFLogxK
U2 - 10.1093/braincomms/fcae247
DO - 10.1093/braincomms/fcae247
M3 - Article
C2 - 39165480
AN - SCOPUS:85201903585
SN - 2632-1297
VL - 6
JO - Brain Communications
JF - Brain Communications
IS - 4
M1 - fcae247
ER -