The increment of annexin V-positive microvesicles versus annexin V-negative microvesicles in CSF of an animal model of Alzheimer's disease.

Objective: Extracellular microvesicles (MVs) as a specific signaling molecule have received much attention in nervous system studies. Alterations in the tissue redox status in pathological conditions, such as Alzheimer's disease (AD), facilitate the translocation of cell membrane phosphatidylserine to the outer leaflet and lead to the MVs shedding. Annexin V binds with high affinity to phosphatidylserine. Some arguments exist about whether Annexin V-negative MVs should be considered in pathological conditions.

Material And Method: We compared the kinetics of two phenotypes of Annexin V-positive and Annexin V-negative MVs in the cerebrospinal fluid (CSF) of amyloid-β (Aβ)-treated male Wistar rats with flow cytometry technique. The Aβ was injected bilaterally into the cerebral ventricles. Thioflavin T staining was used to confirm the presence of hippocampal Aβ fibrils two weeks post-Aβ injection. Levels of hippocampal interleukin-1β were assessed as an inflammatory index. The CSF malondialdehyde (MDA) concentration was determined. The cognitive impairment and anxiety behaviors were assessed by object recognition and elevated plus maze tests, respectively.

Results: Elevation of MDA levels and a significant rise in the scoring of IL-1β staining were found in the Aβ group. The Aβ induced anxiogenic behavior, impaired novel object recognition memory, and increased the CSF levels of the total number of MVs. The number of Annexin V-positive MVs was significantly higher than Annexin V-negative MVs in all groups.

Conclusion: Data showed that Annexin V-positive MVs potentially have a significant contribution to the pathophysiology of the Aβ-induced cognitive impairment. To catch a clear image of microvesicle production in pathological conditions, both phenotypes of Annexin V-positive and Annexin V-negative MVs should be analyzed and reported.