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. 2022;87(4):1537-1547.
doi: 10.3233/JAD-220158.

Association Between Plasma Biomarkers of Amyloid, Tau, and Neurodegeneration with Cerebral Microbleeds

Stuart J McCarter  1   2 , Timothy G Lesnick  3 , Val J Lowe  4 , Alejandro A Rabinstein  1 , Scott A Przybelski  3 , Alicia Algeciras-Schimnich  5 , Vijay K Ramanan  1 , Clifford R Jack  4 , Ronald C Petersen  1 , David S Knopman  1 , Bradley F Boeve  1 , Kejal Kantarci  4 , Prashanthi Vemuri  4 , Michelle M Mielke  1   3 , Jonathan Graff-Radford  1
Affiliations

Association Between Plasma Biomarkers of Amyloid, Tau, and Neurodegeneration with Cerebral Microbleeds

Stuart J McCarter et al. J Alzheimers Dis. 2022.

Abstract

Background: Cerebral microbleeds (CMBs) are a common vascular pathology associated with future intracerebral hemorrhage. Plasma biomarkers of amyloid, tau, and neurodegeneration may provide a screening avenue to identify those with CMBs, but evidence is conflicting.

Objective: To determine the association between plasma biomarkers (Aβ40, Aβ42, t-tau, p-tau181, p-tau217, neurofilament light chain (NfL)) and CMBs in a population-based study of aging and whether these biomarkers predict higher signal on Aβ-PET imaging in patients with multiple CMBs.

Methods: 712 participants from the Mayo Clinic Study of Aging with T2* GRE MRI and plasma biomarkers were included. Biomarkers were analyzed utilizing Simoa (Aβ40, Aβ42, t-tau, NfL) or Meso Scale Discovery (p-tau181, p-tau217) platforms. Cross-sectional associations between CMBs, plasma biomarkers and Aβ-PET were evaluated using hurdle models and multivariable regression models.

Results: Among the 188 (26%) individuals with≥1 CMB, a lower plasma Aβ42/Aβ40 ratio was associated with more CMBs after adjusting for covariables (IRR 568.5 95% CI 2.8-116,127). No other biomarkers were associated with risk or number CMBs. In 81 individuals with≥2 CMBs, higher plasma t-tau, p-tau181, and p-tau217 all were associated with higher Aβ-PET signal, with plasma p-tau217 having the strongest predictive value (r2 0.603, AIC -53.0).

Conclusion: Lower plasma Aβ42/Aβ40 ratio and higher plasma p-tau217 were associated with brain amyloidosis in individuals with CMBs from the general population. Our results suggest that in individuals with multiple CMBs and/or lobar intracranial hemorrhage that a lower plasma Aβ42/Aβ40 ratio or elevated p-tau217 may indicate underlying cerebral amyloid angiopathy.

Keywords: Amyloid-β; PiB-PET; biomarker; cerebral microbleed; plasma; tau.

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Figures

Fig. 1.
Fig. 1.
Predicted log(PiB) versus p-tau217 in individuals with ≥ 2 CMBs. Carrier=APOE E4 positive, non-Carrier=APOE E4 negative
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