Abstract
Amyloid β (Aβ) peptide is deposited in the brains of sporadic Alzheimer’s disease (AD) due to impaired vessel-dependent clearance. To understand the mechanisms, we investigated time-dependent cerebrovascular changes in AD model mice. Cerebrovascular and other pathological changes were analyzed in AD model mice (J20 strain) aging from 2 to 9 months by immunostaining. At 2 months, Aβ was only intraneuronal, whereas vessels were positive from 3 months in J20 mice. Compared to wild-type (WT), vessel density was increased at 2 months but decreased at 9 months in J20 mice, claudin-5 levels were decreased, and vascular endothelial growth factor (VEGF) levels were increased in the cortex and hippocampus of J20 mice brain at all time points. Albumin extravasation was evident from 3 months in J20 brains. Collagen 4 was increased at 2 and 3 months. Aquaporin 4 was spread beyond the vessels starting from 3 months in J20, which was restricted around the vessel in wild-type mice. In conclusion, the study showed that an early decrease in claudin-5 was associated with VEGF expression, indicating dysfunction of the blood–brain barrier. Decreased claudin-5 might cause the leakage of blood constituents into the parenchyma that alters astrocyte polarity and its functions.
Funder
internal departmental funding
Subject
General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Cited by
8 articles.
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