Systemic inflammation and blood-based biomarkers of Alzheimer's Disease

Grace Austin¹, Shaun Eslick¹, Jessica J.A. Ferguson², Christopher Oldmeadow³, Manohar L. Garg¹, Ralph Martins¹

¹ Macquarie Medical School, Macquarie University, Macquarie Park, NSW, Australia
² School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, NSW, Australia
³ Clinical Research Design, Information Technology and Statistical Support Unit, HMRI, New Lambton, NSW, Australia

---

INTRODUCTION

• Systemic inflammation is increasingly implicated in Alzheimer's disease (AD) pathogenesis.¹
• Chronic low-grade inflammation may contribute to neuroinflammation, neuronal injury and early AD pathology.²
• The relationship between inflammation markers and blood-based AD biomarkers remains less established, particularly in midlife adults.

---

AIM

This study examined associations between systemic inflammation markers and blood-based AD biomarkers in dementia-free adults.

---

METHODS

• 237-person cross-sectional cohort study.
• Stored plasma (−80°C) samples were analysed for hs-CRP, IL-6 and TNF-α using enzyme-linked immunosorbent assays (ELISA).
• Plasma AD biomarkers Aβ1–40, Aβ1–42, GFAP, NfL and pTau181 were measured using the ultra-sensitive Single Molecule Array (SIMOA) platform.
• Multivariable regression analyses were used to adjust for age and sex.

---

RESULTS

Participant characteristics

• Mean age: 54 ± 10.2 years
• Female: 78%
• Mean BMI: 24.4 kg/m²

Adjusted associations between systemic inflammation and Alzheimer's disease blood biomarkers

• hs-CRP was significantly associated with increased:
  • NfL: β = 0.44 (95% CI 0.14–0.74), P = 0.004
  • GFAP: β = 2.77 (95% CI 1.10–4.43), P < 0.001
• IL-6 was significantly associated with increased:
  • NfL: β = 2.61 (95% CI 1.72–3.49), P < 0.0001
  • GFAP: β = 9.41 (95% CI 3.64–15.19), P = 0.002
• Significant confounders adjusted for were age and sex.
• In crude analyses, TNF-α was significantly associated with NfL only.
• No significant associations were observed between systemic inflammation markers and Aβ1–42/Aβ1–40 or pTau181.

Data presented as adjusted β coefficients and 95% confidence intervals at margins.

---

CONCLUSION

• Findings suggest a pro-inflammatory profile in midlife is associated with blood-based biomarkers of neurodegeneration and astrocyte activation.
• No associations were observed between pro-inflammatory markers and AD biomarkers Aβ1–42/Aβ1–40 or pTau181.

---

SIGNIFICANCE

• Systemic inflammation may represent a modifiable target for dementia prevention and supports the utility of blood biomarkers for early detection.
• Longitudinal randomised controlled trials examining associations between inflammation and AD biomarkers are warranted.

---

SUMMARY

Higher hs-CRP and IL-6 were associated with increased NfL and GFAP, suggesting systemic inflammation may contribute to early neurodegenerative processes in midlife adults.

---

CONTACT

Grace Austin
PhD, B&D (Hons I), APD
Postdoctoral Research Fellow
Macquarie Medical School
Macquarie University, Sydney, Australia

Email: grace.austin@mq.edu.au