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[P2–265]: GLYCEMIC VARIABILITY IN ACUTE ISCHEMIC STROKE AND COGNITIVE OUTCOME
Author(s) -
Lim JaeSung,
Kim Chulho,
Oh Mi Sun,
Suh Sang Won,
Lee ByungChul,
Yu KyungHo
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.918
Subject(s) - medicine , glycemic , diabetes mellitus , stroke (engine) , neuropsychology , logistic regression , odds ratio , cognition , physical therapy , insulin , endocrinology , psychiatry , mechanical engineering , engineering
Background: Chromic inflammation is involved in dysfunction and loss of neurons in neurodegenerative diseases. The complement system is required for activation of microglia, which might induce phagocytosis of Abeta and also neurons in the brain. Activation of the classical complement pathway and the resident microglia in the brain may be related to synapse failure and loss of neurons in pathogenesis of Alzheimer’s disease (AD). We reported the clinical potential of complement C3 (C3), apolipoprotein A1 (apoA1), and transthyretin (TTR) in the assessment of cognitive decline by longitudinal and cross-sectional cohort studies (Alzheimer Dement (Amst) 1: 270-280, 2015). In this study, we measured peripheral levels of both inactivated and activated complement proteins in mild cognitive impairment (MCI), AD, and non-demented healthy control (NDC). Methods: The complement protein is proteolytically cleaved during its activation. We developed immunoassay which differentially detected an inactive (inC3) and active (aC3) forms of C3. Peripheral profiles of them were analyzed immunoassay using specific antibodies raised against each form of C3. We also analyzed complementderived peptides of C3 and C4 in both serum and the brain by LC-MS/MS to assess their clinical potential for evaluation of cognitive impairment. The least absolute shrinkage and selection operator was used to evaluate the combination of multiple biomarkers. Results:A combination of inC3, apoA1, and TTR achieved an area under the curve (AUC) of 0.85 (sensitivity: 75% and specificity: 90%) in MCI vs. NDC, and the combination of aC3/inC3 ratio, apoA1, and TTR improved value of AUC to 0.87 (sensitivity: 90% and specificity: 83%). By LC-MS/MS, we found novel peptide fragments of complement proteins showing clinical potential in diagnosis of MCI and AD. Immunohistochemistry and LC-MS/MS anlyses of serum and the brain tissues, including the hippocampus, frontal lobe, and cerebellum, from definite AD and NDC revealed that levels of fragments of C3 and C4 including novel peptides were significantly elevated in both serum and the brain from AD comparing to NDC subjects. Conclusions:The current study indicates that peripheral profiles of activated fragments and inactivated form of complement proteins are related to cognitive decline in MCI and AD.