Fig 1: Seroprevalence of autoantibodies against neurodegeneration-related antigens across diagnostic groups, illustrating differences in antibody detection frequencies between patients and healthy controls. Chi3Li (A), anti-α-syn (B), anti-TREM2 (C), anti-NSE (D), anti-MBP (E), anti-NFL (F), anti-MCP-1 (G), anti-FUS (H), anti-TDP-43 (I), anti-NGRN (J), anti-GFAP (K), anti-Tau441 (L), anti-Aβ42 (M), and anti-VSNL1 (N) autoantibodies and the percentage of positive patients within the diagnostic group are shown; inconclusive results represent all the samples with optical density indistinguishable from 0 (0+). AD, Alzheimer’s disease; FTD, frontotemporal lobar neurodegeneration; PD, Parkinson’s disease; VD, vascular dementia; MCI, mild cognitive impairment; CTRL, control group. Chi3L1, chitinase-3-like protein 1; α-syn, alpha-synuclein; TREM2, triggering receptor expressed on myeloid cells 2; NSE, neuron-specific enolase; MBP, myelin basic protein; NFL, neurofilament light chain; MCP-1, monocyte chemoattractant protein-1; FUS, fused in sarcoma; TDP-43, TAR DNA-binding protein 43; NRGN, neurogranin; GFAP, glial fibrillary acidic protein; Tau441, full-length tau protein; Aβ42, amyloid-beta 1–42 peptide; VSNL1, visinin-like protein 1.
Fig 2: Relative levels of IgG autoantibodies against Aβ42 (A), Tau441 (B), α-syn (C), FUS (D), TDP-43 (E), VSNL1 (F), NFL (G), MBP (H), TREM2 (I), NSE (J), Chi3Li (K), GFAP (L), MCP-1 (M), and NGRN (N). While most autoantibody levels did not differ substantially between groups, moderate differences were observed for Chi3L1 and α-syn autoantibodies, particularly in individuals with mild cognitive impairment, suggesting a distinct antibody reactivity profile at early disease stages. Data were analyzed semi-quantitatively by categorizing samples according to autoantibody titers (“0” negative, “0+” very low, “+” low “++” moderate, “+++” high), see Methods for cut-offs. Stacked bar plots show the distribution of semi-quantitative autoantibody reactivity categories (0–+++) across diagnostic groups. Group differences were assessed using the Kruskal–Wallis test followed by pairwise comparisons. p-values were adjusted for multiple testing using the Benjamini–Hochberg false discovery rate procedure. Symbols indicating statistical significance (p values FDR-adjusted): * p < 0.05; ** p < 0.01 (see subfigure K). Color coding based on categorization of antigens outlined in Table 2. AD, Alzheimer’s disease; FTD, frontotemporal lobar neurodegeneration; PD, Parkinson’s disease; VD, vascular dementia; MCI, mild cognitive impairment; CTRL, control group. Aβ42, amyloid-beta 1–42 peptide; Tau441, full-length tau protein; α-syn, alpha-synuclein; FUS, fused in sarcoma; TDP-43, TAR DNA-binding protein 43; VSNL1, visinin-like protein 1; NFL, neurofilament light chain; MBP, myelin basic protein; TREM2, triggering receptor expressed on myeloid cells 2; NSE, neuron-specific enolase; Chi3L1, chitinase-3-like protein 1; GFAP, glial fibrillary acidic protein; MCP-1, monocyte chemoattractant protein-1; NRGN, neurogranin.
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