Author(s)

Luis Manuel Castillo¹, Enrique Moreno¹, Yaneth Rodríguez-Agudelo², Mireya Chávez-Oliveros², Zoila Trujillo³, Blanca Espinosa⁴, Emma Rodriguez-Maldonado⁵, Luis Felipe Montaño⁶, Jorge Guevara¹

¹Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, México.
²Departamento de Neuropsicología, Instituto Nacional de Neurología y Neurocirugía, México City, México.
³Geriatra Instituto Nacional de Neurología y Neurocirugía, México City, México.
⁴Laboratorio de Bioquímica, Instituto Nacional de Enfermedades Respiratorias, México City, México.
⁵Departamento de Fisiología, Instituto Nacional de Cardiología, México City, México.
⁶Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, México.

Amyloid-β (Aβ) can induce a chronic inflammatory immune response that is associated, amongst many others, to abnormal glycosylation, inducible nitric oxide synthase (iNOS) and nitric oxide (NO). The relation between development of Mild Cognitive Impairment (MCI) and Alzheimer’s disease progression and these serum markers has not been evaluated. Serum levels of iNOs, NO, TNF-α, IL-1β, IL-6, IL-8, IL-10, and IL-12 are determined with commercially available kits. Sialylation of albumin-free serum patterns is determined by Western blot analysis with Sambucus nigra (specific for sialic acid attached to terminal galactose in α2,6 linkage) lectin. Apolipoprotein E (ApoE) haplotype is determined by Western blot using specific anti-ApoE 2, 3 or 4 antibodies. A mini-mental state examination (MMSE) test is also performed in the 10 MCI patients, 19 Alzheimer’s disease (AD) patients and 46 healthy age-matched controls evaluated. The results show an increase of iNOS in MCI and AD but significantly higher NO concentrations are only found in MCI patients. TNF-α and IL-1β concentrations are the only significantly increased cytokines in MCI patients; no differences between control and MCI or AD patients are found in regard to the other cytokines. An abnormal MMSE test result only correlates with a decrease in serum NO concentration in MCI patients. The terminal sialic acid linkage pattern of serum proteins also shows highly significant differences between MCI and AD patient. ApoE3/4 or 4/4 haplotypes are characteristic of MCI and AD patients. Our results imply that increased serum TNF-α, IL-1β, iNOS, NO and alterations of serum proteins glycosylation patterns in adult individuals with an abnormal MMSE test may serve as an early biomarker of MCI and AD development.

Alzheimer Disease, Mild Cognitive Impairment, Nitric Oxide, Inflammatory Cytokines, Glycosylation, Apolipoprotein E4

Castillo, L. , Moreno, E. , Rodríguez-Agudelo, Y. , Chávez-Oliveros, M. , Trujillo, Z. , Espinosa, B. , Rodriguez-Maldonado, E. , Montaño, L. and Guevara, J. (2015) IL-1β, TNF-α and Sambucus nigra Reactive Serum Proteins as Biomarkers of Mild Cognitive Impairment and Alzheimer Disease Progression. Advances in Alzheimer's Disease, 4, 99-109. doi: 10.4236/aad.2015.44010.