title: Cerebrospinal fluid levels of Alzheimer's disease biomarkers in middle-aged patients with type 1 diabetes.
abstract: OBJECTIVE
  Type 1 diabetes is associated with moderate cognitive decline and cerebral alterations and may lead to an increased risk of dementia, including Alzheimer's disease. This study aimed to investigate the levels of risk markers for Alzheimer's disease in middle-aged patients with type 1 diabetes and controls, and their potential associations with cognitive and cerebral measures.
  
  
  METHODS
  Levels of β-amyloid (Aβ) 42, Tau, phosphorylated Tau (pTau), the soluble form of low-density lipoprotein receptor-related protein 1 (sLRP1) and macrophage colony-stimulating factor (MCSF) were quantified by ELISA in serum and cerebrospinal fluid (CSF) collected from 37 patients with type 1 diabetes and 15 controls. Associations between biomarkers and determinants of cognitive function and white matter integrity were assessed using hierarchical regression analysis controlling for age, HbA1c and estimated intelligence quotient (IQ).
  
  
  RESULTS
  CSF levels of pTau, Aβ42 and LRP1 were higher in patients with type 1 diabetes than in controls (all p < 0.05). There was a trend towards increased Tau levels in patients with type 1 diabetes (p = 0.056), while CSF levels of MCSF were similar between patients with type 1 diabetes and controls. Regression analysis showed that elevated CSF sLRP1 levels were associated with better attention (β = 0.518; p = 0.002) and a better speed of information-processing (β = 0.368; p = 0.034), as well as increased integrity of the white matter of the right inferior fronto-occipital tract (β = 0.395; p = 0.022). Furthermore, elevated Tau levels were associated with decreased integrity of the white matter of right inferior fronto-occipital tract (β = -0.584; p = 0.002).
  
  
  CONCLUSIONS
  CSF levels of biomarkers for Alzheimer's disease are altered in patients with type 1 diabetes compared with controls, but the observed profile does not match the profile characterising pre-Alzheimer's disease patients.
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Centre, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany, margriet.ouwens@ddz.uni-duesseldorf.de.
authors.forename: D Margriet
authors.initials: DM
authors.lastname: Ouwens
authors.forename: Eelco
authors.initials: E
authors.lastname: van Duinkerken
authors.forename: S Niki M
authors.initials: SN
authors.lastname: Schoonenboom
authors.forename: Daniella
authors.initials: D
authors.lastname: Herzfeld de Wiza
authors.forename: Martin
authors.initials: M
authors.lastname: Klein
authors.forename: Larissa
authors.initials: L
authors.lastname: van Golen
authors.forename: Petra J W
authors.initials: PJ
authors.lastname: Pouwels
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Annette C
authors.initials: AC
authors.lastname: Moll
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Snoek
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D016173:Macrophage Colony-Stimulating Factor