TY - JOUR
T1 - Association of plasma biomarkers of amyloid and neurodegeneration with cerebrovascular disease and Alzheimer's disease
AU - Graff-Radford, Jonathan
AU - Mielke, Michelle M.
AU - Hofrenning, Ekaterina I.
AU - Kouri, Naomi
AU - Lesnick, Timothy G.
AU - Moloney, Christina M.
AU - Rabinstein, Alejandro
AU - Cabrera-Rodriguez, Janisse N.
AU - Rothberg, Darren M.
AU - Przybelski, Scott A.
AU - Petersen, Ronald C.
AU - Knopman, David S.
AU - Dickson, Dennis W.
AU - Jack, Clifford R.
AU - Algeciras-Schimnich, Alicia
AU - Nguyen, Aivi T.
AU - Murray, Melissa E.
AU - Vemuri, Prashanthi
N1 - Funding Information:
D.W. Dickson receives research support from the NIH, the DOD, the Tau Consortium, the Target ALS Foundation, Inc., the Rainwater Charitable Foundation, and the American Parkinson Disease Foundation.
Funding Information:
This work supported by the National Institute on Aging of the National Institutes of Health (NIH) under Award Number RF1 AG069052-01A and the NIH ( AG006786 , AG011378 , NS097495 , AG016574 , AG041851 , AG054449 , AG034676 ), and the GHR Foundation. The funders had no role in the conception or preparation of this manuscript.
Funding Information:
C.R. Jack serves on an independent data monitoring board for Roche, has served as a speaker for Eisai, and consulted for Biogen, but he receives no personal compensation from any commercial entity. He receives research support from NIH and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic.
Funding Information:
M.M. Mielke has consulted for Biogen, Brain Protection Company, and LabCorp. She receives research support from NIH and DOD.
Publisher Copyright:
© 2022
PY - 2022/11
Y1 - 2022/11
N2 - The objective of this study was to determine the differential mapping of plasma biomarkers to postmortem neuropathology measures. We identified 64 participants in a population-based study with antemortem plasma markers (amyloid-β [Aβ] x-42, Aβx-40, neurofilament light [NfL], and total tau [T-tau]) who also had neuropathologic assessments of Alzheimer's and cerebrovascular pathology. We conducted weighted linear-regression models to evaluate relationships between plasma measures and neuropathology. Higher plasma NfL and Aβ42/40 ratio were associated with cerebrovascular neuropathologic scales (p < 0.05) but not with Braak stage, neuritic plaque score, or Thal phase. Plasma Aβ42/40 and NfL explained up to 18% of the variability in cerebrovascular neuropathologic scales. In participants predominantly with modest levels of Alzheimer's pathologic change, biomarkers of amyloid and neurodegeneration were associated with cerebrovascular neuropathology. NfL is a non-specific marker of brain injury, therefore its association with cerebrovascular neuropathology was expected. The association between elevated Aβ42/40 and cerebrovascular disease pathology needs further investigation but could be due to the use of less specific amyloid-β assays (x-40, x-42).
AB - The objective of this study was to determine the differential mapping of plasma biomarkers to postmortem neuropathology measures. We identified 64 participants in a population-based study with antemortem plasma markers (amyloid-β [Aβ] x-42, Aβx-40, neurofilament light [NfL], and total tau [T-tau]) who also had neuropathologic assessments of Alzheimer's and cerebrovascular pathology. We conducted weighted linear-regression models to evaluate relationships between plasma measures and neuropathology. Higher plasma NfL and Aβ42/40 ratio were associated with cerebrovascular neuropathologic scales (p < 0.05) but not with Braak stage, neuritic plaque score, or Thal phase. Plasma Aβ42/40 and NfL explained up to 18% of the variability in cerebrovascular neuropathologic scales. In participants predominantly with modest levels of Alzheimer's pathologic change, biomarkers of amyloid and neurodegeneration were associated with cerebrovascular neuropathology. NfL is a non-specific marker of brain injury, therefore its association with cerebrovascular neuropathology was expected. The association between elevated Aβ42/40 and cerebrovascular disease pathology needs further investigation but could be due to the use of less specific amyloid-β assays (x-40, x-42).
KW - Cerebrovascular neuropathology
KW - Neurodegenerative biomarkers
KW - Neurofilament light (NfL)
KW - Plasma biomarkers
KW - Postmortem neuropathology
KW - Total tau (T-tau)
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UR - http://www.scopus.com/inward/citedby.url?scp=85135692527&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2022.07.006
DO - 10.1016/j.neurobiolaging.2022.07.006
M3 - Article
C2 - 35952440
AN - SCOPUS:85135692527
SN - 0197-4580
VL - 119
SP - 1
EP - 7
JO - Neurobiology of aging
JF - Neurobiology of aging
ER -