To evaluate differences in nervous system proteins and inflammatory cytokines in Alzheimer’s disease (AD) plasma samples relative to healthy control plasma, and determine correlative relationships between the different protein classes.

Alzheimer’s disease is the most significant form of dementia associated with aging. Changes in blood levels of nervous system proteins and inflammatory cytokines are associated with brain cellular damage, and are actively being explored as prognostic/diagnostic biomarkers of AD. 

NF-L, t-Tau, p-Tau181, Aβ1-42, Aβ1-40, GFAP, IL-6, IL-10, and TNFα were analyzed using Quanterix Simoa assays in AD plasma (n=95) and healthy control plasma (n=64). AD sample groups consisted of mild (n=30, MMSE >23-30), moderate (n=24, MMSE=16-22) and severe (n=40, MMSE<16) cognitively impairment.  Differences in each of the plasma proteins within control and AD patient subgroups were evaluated together (Kruskal-Wallis) or pairwise (Mann-Whitney).

Analysis of NF-L, t-Tau, p-Tau181, IL-6, IL-10, and TNFα, revealed significant increases in median levels in the combined AD group (n=72; p<0.0001), relative to controls (n=64).  The plasma Aβ1-42/Aβ1-40 ratio trended lower in the combined AD group but was not significant (p=0.167).  The levels of all biomarkers are elevated in the moderate and severe AD patient subgroups relative to controls (p<0.0001).  Levels of NF-L, p-Tau181, and GFAP were significantly elevated in mild AD relative to controls (p<0.0001) although distributions overlap.  The plasma neurodegenerative biomarkers NF-L, p-Tau181, and t-Tau were significantly correlated to each other in the AD group (Spearman r=0.5-0.7, p<0.0001) as were the three cytokines (IL-6, IL-10, TNFα: r=0.5-0.7; p<0.0001). The strongest group cross-correlations were between NF-L and t-Tau, and the cytokines (r=0.5-0.66, p<0.0001).

Markers of both nervous system damage and inflammation were significantly elevated in the plasma of mild, moderate, and severe AD groups.  A combination of plasma neurodegenerative and inflammatory cytokine biomarkers may effectively identify AD patients.