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Interaction between APOE-ɛ4 and HMGB1 is associated with widespread cortical thinning in mild cognitive impairment
  1. Heidi Foo1,
  2. Kok Pin Ng1,
  3. Jayne Tan1,
  4. Lina Lim2,
  5. Russell Jude Chander1,
  6. Ting Ting Yong1,
  7. Nagaendran Kandiah1,3
  1. 1Department of Neurology, National Neuroscience Institute, Singapore
  2. 2Department of Physiology, Centre for Life Sciences, Singapore
  3. 3Duke-NUS Medical School, Singapore
  1. Correspondence to Dr Nagaendran Kandiah, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore; nagaendran_kandiah{at}nni.com.sg

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Biomarkers which allow for identification of the underlying aetiology of mild cognitive impairment (MCI) are of prognostic importance. In addition to the amyloid-β and hyperphosphorylated tau pathology, genetic factors such as apolipoprotein E (APOE)-ε4 and neuroinflammation may have additional roles in the pathogenesis of Alzheimer's Disease (AD). In this study, we investigated the influence of APOE-ɛ4 status, neuroinflammation as measured by high mobility group box 1 protein (HMGB1), and their interaction effect on cortical thickness in MCI. We hypothesised that the interaction between APOE-ɛ4 and HMGB1 would result in a more widespread pattern of cortical thinning compared with either one factor alone.

Fifty-two individuals (27 mild cognitive impairment (MCI) and 25 controls) were recruited from a tertiary neurological centre. MCI was clinically diagnosed using the National Institute on Aging and the Alzheimer's Association workgroup (NIA-AA) criteria.1 They had a Clinical Dementia Rating (CDR) score of 0.5 and had no other disease that could account for their cognitive deficits. Subjects with active systemic inflammatory states including infections, recent surgery or acute strokes and those receiving anti-inflammatory or cancer treatment were excluded as they could affect the levels of high mobility group box 1 protein (HMGB1). This study was approved by the SingHealth Institutional Ethics Review Board and written informed consent was obtained for all.

Blood samples were collected from all subjects. Genomic DNA was extracted from peripheral blood with QIAamp DNA Blood Maxi Kit (Qiagen, Hilden, Germany). Genotyping for apolipoprotein E (APOE) was performed as described previously.2 Subjects with at least a single copy of …

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