29 used a dual-pathology model to investigate the cross talk between hypertension and AD in the APP/PS1 mouse and showed that hypertensive APP/PS1 mice have a deficit in episodic-like memory tasks, which was associated with increased amyloid deposits and decreased microvascular density in the cortex, the medial prefrontal cortex, and the hippocampus. 14, 27, 28 Understanding how brain vasculature is modified with AD as a function of age could help underpin these associations. 24 – 26Ī correlation between vascular health and Alzheimer’s disease (AD) risk has also been established, with a higher probability of developing AD following exposure to vascular factors such as hypertension or vascular dementia caused by strokes.
It is not yet clear if there are causal effects or if common processes are involved in the pathophysiology. 13, 17 – 23 However, exploring the pathogenesis of vascular changes and cognitive impairment beyond the above associations remains difficult and subject to interpretation.
2 – 13 An association has also been established between vascular disorders, such as hypertension, elevated cholesterol, atherosclerosis, and cognitive impairments, 14 – 16 and also between cardiovascular risk factors, and WM lesions. 1 Considerable evidence is accumulating supporting an association between WM lesions and specific cognitive dysfunctions and/or dementia severity. Recent findings have challenged this idea, suggesting disturbances in white matter (WM) to be a key factor as well. This study supports previous observations that AD transgenic mice show a higher VD in specific regions compared with WT mice during the early and late stages of the disease (4.5 to 8 months), extending results to whole brain mapping.Ĭognitive impairment was long believed to be primarily due to decreased synaptic density and neuron loss. We report a general loss of VD caused by the aging process with a small VD increase in the diseased animals in the somatomotor and somatosensory cortical regions and the olfactory bulb, partly supported by MRI perfusion data. Focusing on the medial prefrontal cortex, cerebral cortex, the olfactory bulb, and the hippocampal formation, we compared the VD of three age groups (2-, 4.5-, and 8-months-old), for both wild type mice and a transgenic model (APP/PS1) with pathology resembling Alzheimer’s disease (AD). Vascular density (VD) was computed using automatic segmentation combined with coregistration techniques to build a group-level vascular metric in the whole brain.
Lefebvre et al human brain mapping serial#
We explore the feasibility of using an automated serial two-photon microscope to image fluorescent gelatin-filled whole rodent brains in three-dimensions (3-D) with the goal of carrying group studies. Abstract Given known correlations between vascular health and cognitive impairment, the development of tools to image microvasculature in the whole brain could help investigate these correlations.
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