Saltar al contenido
Merck

The Alzheimer's disease risk factor CD2AP maintains blood-brain barrier integrity.

Human molecular genetics (2015-09-12)
J Nicholas Cochran, Travis Rush, Susan C Buckingham, Erik D Roberson
RESUMEN

CD2-associated protein (CD2AP) is a leading genetic risk factor for Alzheimer's disease, but little is known about the function of CD2AP in the brain. We studied CD2AP(-/-) mice to address this question. Because CD2AP(-/-) mice normally die by 6 weeks from nephrotic syndrome, we used mice that also express a CD2AP transgene in the kidney, but not brain, to attenuate this phenotype. CD2AP-deficient mice had no behavioral abnormalities except for mild motor and anxiety deficits in a subset of CD2AP(-/-) mice exhibiting severe nephrotic syndrome, associated with systemic illness. Pentylenetetrazol (PTZ)-induced seizures occurred with shorter latency in CD2AP(-/-) mice, but characteristics of these seizures on electroencephalography were not altered. As CD2AP is expressed in brain-adjacent endothelial cells, we hypothesized that the shorter latency to seizures without detectably different seizure characteristics may be due to increased penetration of PTZ related to compromised blood-brain barrier integrity. Using sodium fluorescein extravasation, we found that CD2AP(-/-) mice had reduced blood-brain barrier integrity. Neither seizure severity nor blood-brain barrier integrity was correlated with nephrotic syndrome, indicating that these effects are dissociable from the systemic illness associated with CD2AP deficiency. Confirming this dissociation, wild-type mice with induced nephrotic syndrome maintained an intact blood-brain barrier. Taken together, our results support a role of CD2AP in mediating blood-brain barrier integrity and suggest that cerebrovascular roles of CD2AP could contribute to its effects on Alzheimer's disease risk.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Anti-α-tubulina monoclonal antibody produced in mouse, ascites fluid, clone B-5-1-2
Sigma-Aldrich
Fluorescein sodium salt, used as fluorescent tracer
Sigma-Aldrich
Anti-CD2AP antibody produced in rabbit, Ab2, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution