tetano
Editor, Senior Moderator
Brain Behav Immun Health
. 2025 Apr 30:46:101007.
doi: 10.1016/j.bbih.2025.101007. eCollection 2025 Jul. Comparison of cerebrospinal fluid biomarkers in patients with severe COVID-19 neurological outcomes and Alzheimer's disease
Fernanda G Q Barros-Aragão[SUP] 1 2 3 [/SUP], Thaís L Pinheiro[SUP] 1 3 [/SUP], Talita P Pinto[SUP] 1 [/SUP], Bart Vanderborgh[SUP] 1 [/SUP], Nathane B S Rezende[SUP] 1 [/SUP], Guilherme B de Freitas[SUP] 1 2 3 [/SUP], Gabriel R de Freitas[SUP] 1 [/SUP], Fernando A Bozza[SUP] 1 [/SUP], Andrea S Souza[SUP] 1 [/SUP], Erika C Rodrigues[SUP] 1 [/SUP], Carlos O Brandão[SUP] 4 [/SUP], Paulo Mattos[SUP] 1 [/SUP], Felipe K Sudo[SUP] 1 [/SUP], Fernanda F Tovar-Moll[SUP] 1 [/SUP], Fernanda G De Felice[SUP] 1 2 3 [/SUP]
Affiliations
Background: COVID-19 induces acute and long-term neurological symptoms. Links between COVID-19 neurological disturbance and Alzheimer's disease (AD) have been hypothesized because neuroinflammation plays a significant role in both diseases. However, it is unknown if COVID-19 patients with neurological disturbance present molecular alterations related to AD pathology. A better understanding of possible molecular links between COVID-19-induced neurological disease and AD would lead to improved patient follow-up and late-onset disease prevention. Here, we analyze early AD biomarkers in a Brazilian cohort of COVID-19 patients with neurological symptoms. We compared COVID-19 patients' neuroinflammatory and AD biomarker levels to controls, amnestic mild cognitive impairment (aMCI), and AD.
Methods: We analyzed cerebrospinal (CSF) biomarkers of neuroinflammation (interleukin-6 (IL6)), amyloid-beta (Aβ) proteinopathy (Aβ42/40), phosphorylated Tau (pTau181), and the neurodegeneration-associated biomarker total Tau in controls (n = 36), COVID-19 patients presenting neurological alterations (n = 35), aMCI (n = 19), and AD patients (n = 20). Comparisons were corrected by possible sex, age, and comorbidities confounding effects. CSF biomarkers were correlated with systemic and neuro-inflammation markers.
Results: We found that severe COVID-19 patients presented higher CSF Tau than controls, comparable to alterations observed in AD patients. However, we did not find changes in CSF Aβ42/40, pTau-181/Aβ42, or Tau/Aβ42 ratios. Severe COVID-19 patients presented higher Tau, Tau/Aβ42, and pTau181/Aβ42 than mild patients. In COVID-19 patients, CSF pro-inflammatory cytokine IL6 and AD biomarkers correlated with systemic inflammatory index (SII).
Conclusions: Collectively, our findings reveal that CSF tau levels are comparably elevated in COVID-19 neurological patients and AD, suggesting ongoing neurodegeneration in COVID-19 neurological disease, but no biomarker alterations related to AD pathology. Furthermore, CNS AD-related biomarker levels in COVID-19 patients change in association with disease severity and systemic inflammation. Considering that inflammation may persist post-COVID, our findings urge the assessment of possible AD-related biomarker changes in COVID-19 survivors with lingering symptoms.
Keywords: ATN; Alzheimer; Biomarkers; Coronavirus; Dementia; Long-COVID; Neuroinflammation.
. 2025 Apr 30:46:101007.
doi: 10.1016/j.bbih.2025.101007. eCollection 2025 Jul. Comparison of cerebrospinal fluid biomarkers in patients with severe COVID-19 neurological outcomes and Alzheimer's disease
Fernanda G Q Barros-Aragão[SUP] 1 2 3 [/SUP], Thaís L Pinheiro[SUP] 1 3 [/SUP], Talita P Pinto[SUP] 1 [/SUP], Bart Vanderborgh[SUP] 1 [/SUP], Nathane B S Rezende[SUP] 1 [/SUP], Guilherme B de Freitas[SUP] 1 2 3 [/SUP], Gabriel R de Freitas[SUP] 1 [/SUP], Fernando A Bozza[SUP] 1 [/SUP], Andrea S Souza[SUP] 1 [/SUP], Erika C Rodrigues[SUP] 1 [/SUP], Carlos O Brandão[SUP] 4 [/SUP], Paulo Mattos[SUP] 1 [/SUP], Felipe K Sudo[SUP] 1 [/SUP], Fernanda F Tovar-Moll[SUP] 1 [/SUP], Fernanda G De Felice[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 40417395
- PMCID: PMC12099766
- DOI: 10.1016/j.bbih.2025.101007
Background: COVID-19 induces acute and long-term neurological symptoms. Links between COVID-19 neurological disturbance and Alzheimer's disease (AD) have been hypothesized because neuroinflammation plays a significant role in both diseases. However, it is unknown if COVID-19 patients with neurological disturbance present molecular alterations related to AD pathology. A better understanding of possible molecular links between COVID-19-induced neurological disease and AD would lead to improved patient follow-up and late-onset disease prevention. Here, we analyze early AD biomarkers in a Brazilian cohort of COVID-19 patients with neurological symptoms. We compared COVID-19 patients' neuroinflammatory and AD biomarker levels to controls, amnestic mild cognitive impairment (aMCI), and AD.
Methods: We analyzed cerebrospinal (CSF) biomarkers of neuroinflammation (interleukin-6 (IL6)), amyloid-beta (Aβ) proteinopathy (Aβ42/40), phosphorylated Tau (pTau181), and the neurodegeneration-associated biomarker total Tau in controls (n = 36), COVID-19 patients presenting neurological alterations (n = 35), aMCI (n = 19), and AD patients (n = 20). Comparisons were corrected by possible sex, age, and comorbidities confounding effects. CSF biomarkers were correlated with systemic and neuro-inflammation markers.
Results: We found that severe COVID-19 patients presented higher CSF Tau than controls, comparable to alterations observed in AD patients. However, we did not find changes in CSF Aβ42/40, pTau-181/Aβ42, or Tau/Aβ42 ratios. Severe COVID-19 patients presented higher Tau, Tau/Aβ42, and pTau181/Aβ42 than mild patients. In COVID-19 patients, CSF pro-inflammatory cytokine IL6 and AD biomarkers correlated with systemic inflammatory index (SII).
Conclusions: Collectively, our findings reveal that CSF tau levels are comparably elevated in COVID-19 neurological patients and AD, suggesting ongoing neurodegeneration in COVID-19 neurological disease, but no biomarker alterations related to AD pathology. Furthermore, CNS AD-related biomarker levels in COVID-19 patients change in association with disease severity and systemic inflammation. Considering that inflammation may persist post-COVID, our findings urge the assessment of possible AD-related biomarker changes in COVID-19 survivors with lingering symptoms.
Keywords: ATN; Alzheimer; Biomarkers; Coronavirus; Dementia; Long-COVID; Neuroinflammation.