Contactin-2, a synaptic and axonal protein, is reduced in cerebrospinal fluid and brain tissue in Alzheimer’s disease

Autor: Madhurima Chatterjee, Marta Del Campo, Tjado H. J. Morrema, Matthijs de Waal, Wiesje M. van der Flier, Jeroen J. M. Hoozemans, Charlotte E. Teunissen
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Alzheimer’s Research & Therapy, Vol 10, Iss 1, Pp 1-11 (2018)
Druh dokumentu: article
ISSN: 1758-9193
DOI: 10.1186/s13195-018-0383-x
Popis: Abstract Background Synaptic and axonal loss are two major mechanisms underlying Alzheimer’s disease (AD) pathogenesis, and biomarkers reflecting changes in these cellular processes are needed for early diagnosis and monitoring the progression of AD. Contactin-2 is a synaptic and axonal membrane protein that interacts with proteins involved in the pathology of AD such as amyloid precursor protein (APP) and beta-secretase 1 (BACE1). We hypothesized that AD might be characterized by changes in contactin-2 levels in the cerebrospinal fluid (CSF) and brain tissue. Therefore, we aimed to investigate the levels of contactin-2 in the CSF and evaluate its relationship with disease pathology. Methods Contactin-2 was measured in CSF from two cohorts (selected from the Amsterdam Dementia Cohort), comprising samples from controls (cohort 1, n = 28; cohort 2, n = 20) and AD (cohort 1, n = 36; cohort 2, n = 70) using an analytically validated commercial enzyme-linked immunosorbent assay (ELISA). The relationship of contactin-2 with cognitive decline (Mini-Mental State Examination (MMSE)) and other CSF biomarkers reflecting AD pathology were analyzed. We further characterized the expression of contactin-2 in postmortem AD human brain (n = 14) versus nondemented controls (n = 9). Results CSF contactin-2 was approximately 1.3-fold reduced in AD patients compared with controls (p
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