TY - JOUR
T1 - Associations of Neurodegeneration Biomarkers in Cerebrospinal Fluid with Markers of Alzheimer's Disease and Vascular Pathology
AU - Shir, Dror
AU - Mielke, Michelle M.
AU - Hofrenning, Ekaterina I.
AU - Lesnick, Timothy G.
AU - Knopman, David S.
AU - Petersen, Ronald C.
AU - Jack, Clifford R.
AU - Algeciras-Schimnich, Alicia
AU - Vemuri, Prashanthi
AU - Graff-Radford, Jonathan
N1 - Funding Information:
M.M. Mielke served as a consultant to Brain Protection Company, Biogen, and LabCorp and receives research support from the National Institutes of Health and the Department of Defense. She is a Senior Associate Editor for Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association. She is an Editorial Board Member of this journal but was not involved in the peer-review process nor had access to any information regarding its peer-review.
Funding Information:
C.R. Jack serves on an independent data monitoring board for Roche, but he receives no personal compensation from any commercial entity. He receives research support from the National Institutes of Health, the GHR Foundation and the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic.
Funding Information:
D.S. Knopman serves on a Data Safety Monitoring Board for Biogen (fee paid to institution), the DIAN-TU study (receives personal consulting fees), Agenbio (unpaid), and an endovascular carotid reconstruction study (unpaid). He is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the Alzheimer’s Disease Cooperative Study, and receives research support from the National Institutes of Health and philanthropic funds. He is an Editorial Board Member of this journal but was not involved in the peer-review process nor had access to any information regarding its peer-review.
Funding Information:
V. J. Lowe consults for Bayer Schering Pharma, Piramal Life Sciences, Life Molecular Imaging, Eisai Inc., AVID Radiopharmaceuticals, and Merck Research and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals and the NIH (NIA, NCI). A. Algeciras-Schimnich participates in advisory boards for Roche Diagnostics, Fujirebio Diagnostics and Siemens.
Funding Information:
This study was supported by funding from the National Institutes of Health (RF1 AG069052-01A1, U01 AG006786, R37 AG011378, R01 041851, R01 NS097495, and P30 AG062677) and the GHR Foundation. This study was made possible using the resources of the Rochester Epidemiology Project, which is supported by the National Institute on Aging of the National Institutes of Health under Award Number R01 AG034676.
Funding Information:
P. Vemuri received speaking fees from Miller Medical Communications, LLC, and receives research support from the National Institutes of Health.
Publisher Copyright:
© 2023 - IOS Press. All rights reserved.
PY - 2023
Y1 - 2023
N2 - Background: The National Institute on Aging-Alzheimer's Association Research Framework proposes defining Alzheimer's disease by grouping imaging and fluid biomarkers by their respective pathologic processes. The AT(N) structure proposes several neurodegenerative fluid biomarkers (N) including total tau (t-tau), neurogranin (Ng), and neurofilament light chain (NfL). However, pathologic drivers influencing each biomarker remain unclear. Objective: To determine whether cerebrospinal fluid (CSF)-neurodegenerative biomarkers (N) map differentially to Alzheimer's disease pathology measured by Aβ42 (an indicator of amyloidosis, [A]), p-tau (an indicator of tau deposition, [T]), and MRI vascular pathology indicators (measured by white-matter integrity, infarcts, and microbleeds [V]). Methods: Participants were from Mayo Clinic Study of Aging (MCSA) with CSF measures of NfL, Ng, t-tau, Aβ42, and p-tau and available MRI brain imaging. Linear models assessed associations between CSF neurodegeneration (N) markers, amyloid markers (A), tau (T), and vascular pathology (V). Results: Participants (n = 408) had a mean age of 69.2±10.7; male, 217 (53.2%); cognitively unimpaired, 359 (88%). All three neurodegeneration biomarkers correlated with age (p < 0.001 for NfL and t-tau, p = 0.018 for Ng). Men had higher CSF-NfL levels; women had higher Ng (p < 0.001). NfL and t-tau levels correlated with infarcts (p = 0.009, p = 0.034 respectively); no biomarkers correlated with white-matter integrity. N biomarkers correlated with p-tau levels (T, p < 0.001). Higher Aβ42 levels associated with higher N-biomarker levels but only among cognitively unimpaired (A, p < 0.001). Conclusion: The influence of vascular pathology in the general population on CSF (N) biomarkers is modest, with greater influence of infarcts than white-matter disruption. Neurodegeneration markers more closely correlated with tau than amyloid markers.
AB - Background: The National Institute on Aging-Alzheimer's Association Research Framework proposes defining Alzheimer's disease by grouping imaging and fluid biomarkers by their respective pathologic processes. The AT(N) structure proposes several neurodegenerative fluid biomarkers (N) including total tau (t-tau), neurogranin (Ng), and neurofilament light chain (NfL). However, pathologic drivers influencing each biomarker remain unclear. Objective: To determine whether cerebrospinal fluid (CSF)-neurodegenerative biomarkers (N) map differentially to Alzheimer's disease pathology measured by Aβ42 (an indicator of amyloidosis, [A]), p-tau (an indicator of tau deposition, [T]), and MRI vascular pathology indicators (measured by white-matter integrity, infarcts, and microbleeds [V]). Methods: Participants were from Mayo Clinic Study of Aging (MCSA) with CSF measures of NfL, Ng, t-tau, Aβ42, and p-tau and available MRI brain imaging. Linear models assessed associations between CSF neurodegeneration (N) markers, amyloid markers (A), tau (T), and vascular pathology (V). Results: Participants (n = 408) had a mean age of 69.2±10.7; male, 217 (53.2%); cognitively unimpaired, 359 (88%). All three neurodegeneration biomarkers correlated with age (p < 0.001 for NfL and t-tau, p = 0.018 for Ng). Men had higher CSF-NfL levels; women had higher Ng (p < 0.001). NfL and t-tau levels correlated with infarcts (p = 0.009, p = 0.034 respectively); no biomarkers correlated with white-matter integrity. N biomarkers correlated with p-tau levels (T, p < 0.001). Higher Aβ42 levels associated with higher N-biomarker levels but only among cognitively unimpaired (A, p < 0.001). Conclusion: The influence of vascular pathology in the general population on CSF (N) biomarkers is modest, with greater influence of infarcts than white-matter disruption. Neurodegeneration markers more closely correlated with tau than amyloid markers.
KW - Alzheimer's disease
KW - amyloid
KW - cerebrospinal fluid
KW - neurodegeneration
KW - neurofilament light chain
KW - neurogranin
KW - total tau
KW - white matter integrity
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U2 - 10.3233/JAD-221015
DO - 10.3233/JAD-221015
M3 - Article
C2 - 36806507
AN - SCOPUS:85152173279
SN - 1387-2877
VL - 92
SP - 887
EP - 898
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 3
ER -