Stereological Changes in Microvascular Parameters in Hippocampus of a Transgenic Rat Model of Alzheimer's Disease
Abstract
Background: Microcirculatory factors play an important role in amyloid-β (Aβ)-related neuropathology in Alzheimer's disease (AD). Transgenic (Tg) rat models of mutant Aβ deposition can enhance our understanding of this microvascular pathology.
Objective: Here we report stereology-based quantification and comparisons (between- and within-group) of microvessel length and number and associated parameters in hippocampal subregions in Tg model of AD in Fischer 344 rats and non-Tg littermates. Methods: Systematic-random samples of tissue sections were processed and laminin immunostained to visualize microvessels through the entire hippocampus in Tg and non-Tg rats.
A computer-assisted stereology system was used to quantify microvessel parameters including total number, total length, and associated densities in dentate gyrus (DG) and cornu ammonis (CA) subregions. Results: Thin hair-like capillaries are common near Aβ plaques in hippocampal subregions of Tg rats.
There are a 53% significant increase in average length per capillary across entire hippocampus (p<=0.04) in Tg compared to non-Tg rats; 49% reduction in capillary length in DG (p<=0.02); and, higher microvessel density in principal cell layers (p<=0.03). Furthermore, within-group comparisons confirm Tg but not non-Tg rats have significant increase in number density (p<=0.01) and potential diffusion distance (p<=0.04) of microvessels in principal cell layers of hippocampal subregions.
Conclusion: We show the Tg deposition of human Aβ mutations in rats disrupts the wild-type microanatomy of hippocampal microvessels. Stereology-based microvascular parameters could promote the development of novel strategies for protection and the therapeutic management of AD.