Cerebrospinal fluid levels of Alzheimer's disease biomarkers in middle-aged patients with type 1 diabetes.

Abstract

AIMS/HYPOTHESIS:

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/INTERPRETATION:

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: D Margriet Ouwens, Eelco van Duinkerken, S Niki M Schoonenboom, Daniella Herzfeld de Wiza, Martin Klein, Larissa van Golen, Petra J W Pouwels, Frederik Barkhof, Annette C Moll, Frank J Snoek, Charlotte E Teunissen, Philip Scheltens, Michaela Diamant
• Journal: Diabetologia (Diabetologia) Vol. 57 Issue 10 Pg. 2208-14 (Oct 2014) ISSN: 1432-0428 [Electronic] Germany
• PMID: 25034377 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Biomarkers
• LRP1 protein, human
• Low Density Lipoprotein Receptor-Related Protein-1
• Peptide Fragments
• amyloid beta-protein (1-42)
• tau Proteins
• Macrophage Colony-Stimulating Factor

Topics

• Adult
• Alzheimer Disease (metabolism)
• Amyloid beta-Peptides (metabolism)
• Biomarkers (cerebrospinal fluid)
• Cross-Sectional Studies
• Diabetes Mellitus, Type 1 (metabolism)
• Genotype
• Humans
• Low Density Lipoprotein Receptor-Related Protein-1 (metabolism)
• Macrophage Colony-Stimulating Factor (metabolism)
• Middle Aged
• Peptide Fragments (metabolism)
• tau Proteins (metabolism)