Abstract
IntroductionTo quantitatively investigate the capillaries within the white matter of Tg2576 Alzheimer's disease (AD) transgenic mice during the early stage.MethodsIn the current study, 10‐month‐old male Tg2576 AD mice were used as the early‐stage AD group and age‐matched nontransgenic littermate mice were used as the wild‐type group. Then, the Morris water maze was used to examine the spatial learning and memory abilities of the mice in both groups, and unbiased stereological methods were used to accurately quantify the volume of white matter and the parameters of the capillaries within the white matter, such as the total length, total volume, and total surface area of capillaries.ResultsThe Morris water maze performance of the Tg2576 group was worse than that of the wild‐type group, while the white matter volume did not significantly differ between the wild‐type group and the Tg2576 group. The total length, total volume, and total surface area of the capillaries within the white matter of the Tg2576 group were significantly decreased compared to those of the wild‐type group.ConclusionsThe current study provide structural basis for understanding the pathological changes of the early stage of AD and cognitive decline in AD might be associated with changes in the white matter capillaries. Capillaries within the white matter might, thus, serve as a valid target for the prevention and treatment of early‐stage AD.
Highlights
To quantitatively investigate the capillaries within the white matter of Tg2576 Alzheimer's disease (AD) transgenic mice during the early stage
The results showed that the geometric parameters of the capillaries within the white matter of 10‐month‐old Tg2576 AD mice, such as total length, total volume, and total surface area of capillaries in the white matter, were signifi‐ cantly lower than those in the wild‐type mice of the same age
Lee et al calculated the capillaries in the corpus callosums of 7‐month‐old AD mice, while we calcu‐ lated the capillaries in the white matter at the age of 10 months be‐ cause our previous study found that behavioral changes in AD mice began at 10 months (Zhang et al, 2013)
Summary
Alzheimer's disease (AD) is a common neurodegenerative disease in clinical settings that is characterized by progressive memory deficits and cognitive disorder (Querfurth & LaFerla, 2010). Studies have shown that pathological changes in capillaries in the brain play an extremely important role in the pathogenesis of this devastating dis‐ ease (Østergaard et al, 2013; de la Torre, 2002b). Cerebral capillary degeneration, included looping, twining, and braiding of vessels, has been shown to be present in pathologi‐ cally confirmed cases of AD (Farkas & Luiten, 2001; Østergaard et al, 2013) These pathological changes have been shown to cause brain capillary microcirculation deficits and brain hypoperfusion, which could lead to both cognitive and memory decline in AD (Attems & Jellinger, 2004; Oshima et al, 2006). No study has quantified the capillary pathological changes in the white matter of early stage in AD patients or AD models. The pres‐ ent study could provide an accurate quantitative method‐ ological design for future studies on the capillaries changes in the AD white matter, and provide a structural basis for capillary pathological changes in the white matter during early‐stage AD
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