Sign up for email alert when new content gets added: Sign up
Objectives: Neuropathological evaluations are the gold standard for diagnosing a patient’s neurodegenerative disease and for validating biomarker tests. However, there may be a long delay between a biomarker determination and death. Plasma biomarker assays may provide a useful probabilistic determination of the identity of the causative condition and may easily be standardized across clinics. Unfortunately, validations of antemortem plasma biomarkers with postmortem neuropathology are rare. In this work, plasma was obtained from the Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program (AZSAND/BBDP) a longitudinal clinicopathological study that collects plasma antemortem and conducts autopsies after death.
Methods: Plasma samples were collected from 1 to 1.5 years before death. Biomarkers, including Aβ1-40, Aβ1-42, T-Tau, pTau181, α-synuclein, TDP-43, etc., in plasma were assayed using Immunomagnetic Reduction (IMR). Postmortem semi-quantitative histological assessments were done of the regional brain distributions of amyloid plaques, Neurofibrillary Tangles (NFT), Lewy-Type Synucleinopathy (LTS) and TDP proteinopathy.
Results: The levels of T-Tau and Aβ1-42xT-Tau can be used to estimate the histopathological brain loads of all of these. Plasma pTau181/TDP-43 predicts the regional and total brain NFT densities. Plasma α-synuclein levels positively correlate with LTS total brain load. Significantly higher levels of plasma TDP-43 were detected in subjects with histopathological TDP-43 pathology as compared to TDP-43-negative subjects.
Conclusion: These results demonstrate the significant relationships between antemortem plasma biomarkers and postmortem neuropathology.
+44 73620 49920
