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

•A population-based study, mostly without dementia or modest Alzheimer's pathology.•Antemortem plasma NfL and Aβ42/40 correlate with cerebrovascular neuropathy scales.•Plasma T-tau did not correlate with any neuropathologic assessment.•Unspecific amyloid-β assays may link elevated Aβ42/40 with...

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Published in:Neurobiology of aging 2022-11, Vol.119, p.1-7
Main Authors: Graff-Radford, Jonathan, Mielke, Michelle M., Hofrenning, Ekaterina I., Kouri, Naomi, Lesnick, Timothy G., Moloney, Christina M., Rabinstein, Alejandro, Cabrera-Rodriguez, Janisse N., Rothberg, Darren M., Przybelski, Scott A., Petersen, Ronald C., Knopman, David S., Dickson, Dennis W., Jack, Clifford R., Algeciras-Schimnich, Alicia, Nguyen, Aivi T., Murray, Melissa E., Vemuri, Prashanthi
Format: Article
Language:English
Subjects:
Alzheimer Disease - pathology
Amyloid
Amyloid beta-Peptides
Amyloidosis
Biomarkers
Cerebrovascular Disorders
Cerebrovascular neuropathology
Humans
Neurodegenerative biomarkers
Neurofilament light (NfL)
Plaque, Amyloid - pathology
Plasma biomarkers
Postmortem neuropathology
tau Proteins
Total tau (T-tau)
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Summary:•A population-based study, mostly without dementia or modest Alzheimer's pathology.•Antemortem plasma NfL and Aβ42/40 correlate with cerebrovascular neuropathy scales.•Plasma T-tau did not correlate with any neuropathologic assessment.•Unspecific amyloid-β assays may link elevated Aβ42/40 with cerebrovascular pathology.•Cerebrovascular disease impact on plasma biomarker concentration needs more study. 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).
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2022.07.006