Abstract
The validity of amyloid-β peptide (Aβ 1-42) intrahippocampal injection, as an animal model of Alzheimer's disease (AD), has previously been considered in terms of inflammatory reactivity and neuronal damage. In this work, we have extended the testing of the animal model to vasculature by comparison of selected properties of microvessels in vivo with those in human AD brain tissue. The injection of Aβ 1-42, relative to control PBS (phosphate buffered saline), increased the mean number of microvessels and diminished the mean length of microvessels in the molecular layer of dentate gyrus. The animal model showed Aβ 1-42, but not PBS, injection was associated with abnormalities in morphology of microvessels which were characterized as looping, fragmented, knob-like, uneven, and constricted. In particular, numbers of constricted microvessels, defined as vessels with diameters less than 3 μm, were considerably enhanced for Aβ 1-42, compared to PBS, injection. In comparison, human AD brain demonstrated an elevated number of microvessels with a diminished mean length relative to nondemented (ND) brain. Additionally, microvessel perturbations in AD brain showed a similar pattern of morphological abnormalities to those observed in Aβ 1-42-injected rat hippocampus. Constricted microvessels were a prominent feature of AD brain but were rarely observed in ND tissue. These results provide the first evidence that a peptide-injection animal model exhibits a commonality in perturbations of microvessels compared with those evident in AD brain.
Highlights
A host of animal models have been proposed with relevance to modeling the pathological features which characterize Alzheimer’s disease (AD) brain
We have extended the testing of the animal model to vasculature by comparison of selected properties of microvessels in vivo with those in human AD brain tissue
These features involve a broad spectrum of altered properties from those of control nondemented (ND) individuals including the presence of enhanced deposits of amyloid-β peptide (Aβ) [1], neurofibrillary tangles (NFTs) [2], abnormalities in vasculature [3,4,5], evidence for ongoing chronic inflammation [6, 7], and loss of neurons and synaptic connectivity [8]
Summary
A host of animal models have been proposed with relevance to modeling the pathological features which characterize Alzheimer’s disease (AD) brain. In order to test the validity of the animal models, properties and predictions from animal models can be compared with the characteristic features present in AD brains These features involve a broad spectrum of altered properties from those of control nondemented (ND) individuals including the presence of enhanced deposits of amyloid-β peptide (Aβ) [1], neurofibrillary tangles (NFTs) [2], abnormalities in vasculature [3,4,5], evidence for ongoing chronic inflammation [6, 7], and loss of neurons and synaptic connectivity [8]. Intrahippocampal injection of Aβ1−42 in rat brain has been suggested as an animal model which emphasizes the inflammatory reactivity present in human AD brain [9]. This model shows marked enhancement of microgliosis in response to peptide relative to control injections of PBS (phosphate buffered saline) vehicle or reverse peptide (Aβ42−1). Comparison at the molecular and cellular levels has included the finding that enhanced expression of the purinergic ionotropic P2X7 receptor in International Journal of Alzheimer’s Disease activated microglia occurred both in the animal model and in AD brain tissue [13]
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