{
  "abstract": "Systemic infection such as urinary tract infection (UTI) causes delirium and faster cognitive decline in patients with Alzheimer’s disease (AD). Changes in brain cytokine levels in response to systemic infection influence amyloid-β/tau and glial pathology. Here we investigate the relationships between blood cytokines and neurodegenerative biomarkers, UTIs and disease progression in AD. We analysed blood samples from 84 AD patients and 29 elderly controls using two platforms: OLINK®Target-48 Inflammation and ultrasensitive single-molecule array(Simoa®) assay. We stratified AD patients according to the presence/absence of chronic UTIs confirmed on longitudinal urine sampling for urine microscopy and culture.AD patients had elevated NfL, GFAP, p-tau217, and a range of inflammatory proteins. NfL, a marker of axonal injury, correlated with multiple cytokines, including IL-17A, which was also associated with ADAS-Cog scores in mixed-effect models analysis. IL-17A was elevated in AD patients with both, acute and chronic UTIs. The presence of chronic UTIs was associated with higher GFAP, and faster rates of cognitive decline despite matching for age and disease stage (mean ADAS-Cog change 10.6points/year versus 4.81points/year respectively, t=2.31, p<0.05). AD mouse models support the mechanistic link between IL-17A accumulation, cognitive deficits and neurodegeneration. These findings highlight systemic infection as an important contributor to dementia, requiring early identification and treatment in this vulnerable population.m.a.kolanko@gmail.com",
  "authors": [
    {
      "affiliations": [
        "Care Research and Technology Research Group, UK Dementia Research Institute",
        "Brain Sciences Department, Imperial College London"
      ],
      "name": "Kolanko Magdalena"
    },
    {
      "affiliations": [
        "Care Research and Technology Research Group, UK Dementia Research Institute",
        "Infectious Disease Department, Imperial College London"
      ],
      "name": "Jackson Raphaella"
    },
    {
      "affiliations": [
        "Care Research and Technology Research Group, UK Dementia Research Institute",
        "Brain Sciences Department, Imperial College London"
      ],
      "name": "David Michael"
    },
    {
      "affiliations": [
        "Care Research and Technology Research Group, UK Dementia Research Institute",
        "Infectious Disease Department, Imperial College London"
      ],
      "name": "Jensen Kirsten"
    },
    {
      "affiliations": [
        "Care Research and Technology Research Group, UK Dementia Research Institute",
        "Infectious Disease Department, Imperial College London"
      ],
      "name": "Tran Martin"
    },
    {
      "affiliations": [
        "Care Research and Technology Research Group, UK Dementia Research Institute",
        "Surrey and Borders NHS Foundation Trust, UK"
      ],
      "name": "Nilforooshan Ramin"
    },
    {
      "affiliations": [
        "Care Research and Technology Research Group, UK Dementia Research Institute",
        "Brain Sciences Department, Imperial College London"
      ],
      "name": "Wingfield David"
    },
    {
      "affiliations": [
        "Department of Neurodegenerative Disease, UCL Institute of Neurology, UK",
        "Dementia Research Institute at UCL, UK",
        "Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden",
        "Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska"
      ],
      "name": "Zetterberg Henrik"
    },
    {
      "affiliations": [
        "Care Research and Technology Research Group, UK Dementia Research Institute",
        "Infectious Disease Department, Imperial College London"
      ],
      "name": "Freemont Paul"
    },
    {
      "affiliations": [
        "Care Research and Technology Research Group, UK Dementia Research Institute",
        "Brain Sciences Department, Imperial College London"
      ],
      "name": "Sharp David"
    }
  ],
  "title": "241 Relationships between inflammatory cytokines, neurodegenerative biomarkers, clinical progression and systemic infection in alzheimer’s disease",
  "uid": "e67a0a4e-f652-5a0f-98c0-c5d99f9ac26b"
}