Associations of amyloid and neurodegeneration plasma biomarkers with comorbidities

Abstract

Introduction: Blood-based biomarkers of amyloid pathology and neurodegeneration are entering clinical use. It is critical to understand what factors affect the levels of these markers.

Methods: Plasma markers (Aβ42, Aβ40, NfL, T-tau, Aβ42/40 ratio) were measured on the Quanterix Simoa HD-1 analyzer for 996 Mayo Clinic Study of Aging (MCSA) participants, aged 51 to 95 years. All other data were collected during in-person MCSA visits or abstracted from the medical record.

Results: Among cognitively unimpaired (CU) participants, all plasma markers correlated with age. Linear regression models revealed multiple relationships. For example, higher Charlson Comorbidity Index and chronic kidney disease were associated with higher levels of all biomarkers. Some relationships differed between mild cognitive impairment and dementia participants.

Discussion: Multiple variables affect plasma biomarkers of amyloid pathology and neurodegeneration among CU in the general population. Incorporating this information is critical for accurate interpretation of the biomarker levels and for the development of reference ranges.

Keywords: amyloid; cognition; comorbid conditions; demographics; neurofilament light chain; total tau.

FIGURE 1

Boxplots of plasma markers by cognitive diagnosis Abbreviations: Aβ40, Amyloid-beta 40; Aβ42, Amyloid-beta 42; Aβ42/40, Ratio of Amyloid-beta 42 to Amyloid-beta 40; CU, Cognitively Unimpaired; MCI, Mild Cognitive Impairment; NfL, Neurofilament Light Chain; T-tau, Total Tau Protein. P value is from Wilcoxon rank-sum test.

FIGURE 2

Spearman correlation matrix of plasma markers Abbreviations: Aβ40, Amyloid-beta 40; Aβ42, Amyloid-beta 42; Aβ42/40, Ratio of Amyloid-beta 42 to Amyloid-beta 40; APOE, Apolipoprotein E; CU, Cognitively Unimpaired; MCI, Mild Cognitive Impairment; NfL, Neurofilament Light Chain; T-tau, Total Tau Protein.

FIGURE 3

Spearman correlations of plasma markers with age Abbreviations: Aβ40, Amyloid-beta 40; Aβ42, Amyloid-beta 42; Aβ42/40, Ratio of Amyloid-beta 42 to Amyloid-beta 40; CU, Cognitively Unimpaired; MCI, Mild Cognitive Impairment; NfL, Neurofilament Light Chain; T-tau, Total Tau Protein.

FIGURE 4

Forest plots of linear model results adjusted for age and sex Abbreviations: Aβ40, Amyloid-beta 40; Aβ42, Amyloid-beta 42; Aβ42/40, Ratio of Amyloid-beta 42 to Amyloid-beta 40; A+, PiB-PET SUVR ≥ 1.48; AFib, Atrial Fibrillation; APOE, Apolipoprotein E; BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory-II; Beta, Linear Regression Model Coefficient; CI, Confidence Interval; CKD, Chronic Kidney Disease; CU, Cognitively Unimpaired; MCI, Mild Cognitive Impairment; MI, Myocardial Infarction; NfL, Neurofilament Light Chain; T-tau, Total Tau Protein. Models corresponding to the global and domain cognitive z-scores additionally adjust for education.

FIGURE 5

Forest plots of BMI linear model results adjusted for age and sex compared to BMI of 18.5 to 24.9 Abbreviations: Aβ40, Amyloid-beta 40; Aβ42, Amyloid-beta 42; Aβ42/40, Ratio of Amyloid-beta 42 to Amyloid-beta 40; APOE, Apolipoprotein E; Beta, Linear Regression Model Coefficient; BMI, Body Mass Index; CI, Confidence Interval; CU, Cognitively Unimpaired; MCI, Mild Cognitive Impairment; NfL, Neurofilament Light Chain; T-tau, Total Tau Protein.