Association of plasma biomarkers of amyloid and neurodegeneration with cerebrovascular disease and Alzheimer's disease

Jonathan Graff-Radford, Michelle M. Mielke, Ekaterina I. Hofrenning, Naomi Kouri, Timothy G. Lesnick, Christina M. Moloney, Alejandro Rabinstein, Janisse N. Cabrera-Rodriguez, Darren M. Rothberg, Scott A. Przybelski, Ronald C. Petersen, David S. Knopman, Dennis W. Dickson, Clifford R. Jack, Alicia Algeciras-Schimnich, Aivi T. Nguyen, Melissa E. Murray, Prashanthi Vemuri

Research output: Contribution to journalArticlepeer-review


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).

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalNeurobiology of aging
StatePublished - Nov 2022


  • Cerebrovascular neuropathology
  • Neurodegenerative biomarkers
  • Neurofilament light (NfL)
  • Plasma biomarkers
  • Postmortem neuropathology
  • Total tau (T-tau)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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