CSF-ApoER2 fragments as a read-out of reelin signaling: Distinct patterns in sporadic and autosomal-dominant Alzheimer disease
Por:
Lopez-Font I, Iborra-Lazaro G, Sánchez-Valle R, Molinuevo JL, Cuchillo-Ibañez I and Sáez-Valero J
Publicada:
1 mar 2019
Ahead of Print:
12 dic 2018
Resumen:
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.
Filiaciones:
Lopez-Font I:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 Sant Joan d'Alacant, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain
Iborra-Lazaro G:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 Sant Joan d'Alacant, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain
Sánchez-Valle R:
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clinic, 08036 Barcelona, Spain
Molinuevo JL:
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clinic, 08036 Barcelona, Spain
Cuchillo-Ibañez I:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 Sant Joan d'Alacant, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain
:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 Sant Joan d'Alacant, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain
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