Journal
CLINICA CHIMICA ACTA
Volume 490, Issue -, Pages 6-11Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.cca.2018.12.012
Keywords
Reelin; ApoER2; Proteolytic fragment; CSF; Autosomal-dominant AD; Sporadic AD
Categories
Funding
- EU BIOMARKAPD-Joint Programming on Neurodegenerative Diseases (JPND) project
- Instituto de Salud Carlos III (ISCIII) [PI11/03026, PI15/00665, PI08/0036, PI12/00013, PI11/03023]
- Direccio General d'Universitat, Investigacio i Ciencia, GVA [AICO/2018/090]
- Fondo Europeo de Desarrollo Regional (FEDER, Investing in your future)
- CIBERNED, ISCIII
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Reelin is a glycoprotein associated with synaptic plasticity and neurotransmission. The malfunctioning of reelin signaling in the brain is likely to contribute to the pathogenesis of Alzheimer's disease (AD). Reelin binding to Apolipoprotein E receptor 2 (ApoER2) activates downstream signaling and induces the proteolytic cleavage of ApoER2, resulting in the generation of soluble fragments. To evaluate the efficiency of reelin signaling in AD, we have quantified the levels of reelin and soluble ectodomain fragments of ApoER2 (ectoApoER2) in the cerebrospinal fluid (CSF). CSF from sporadic AD patients (sAD; n = 14, age 54-83 years) had lower levels of ectoApoER2 (similar to 31% reduction; p = .005) compared to those in the age-matched controls (n = 10, age 61-80), and a higher reelin/ecto-ApoER2 ratio. In contrast, autosomal dominant AD patients, carriers of PSEN1 mutations (ADAD; n = 7, age 31-49 years) had higher ecto-ApoER2 levels (similar to 109% increment; p = .001) and a lower reelin/ecto-ApoER2 ratio than the non-mutation carriers from the same families (n = 7, age 25-47 years). Our data suggest that the levels of ecto-ApoER2 in CSF could be a suitable read-out of an impaired reelin signaling in AD, but also indicate differences between sAD and ADAD.
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