Alzheimer's disease amyloidogenesis is linked to altered lower urinary tract physiology.
Alzheimer's disease amyloidogenesis is linked to altered lower urinary tract physiology.
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阿尔茨海默病淀粉样蛋白生成与下尿路生理学改变有关。
DOI：
10.1002/nau.24952
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发表时间：
2022
影响因子：
2
通讯作者：
Smith,PhillipP
中科院分区：
文献类型：
--
作者：
Hardy,CaraC;Ramasamy,Ramalakshmi;Rosenberg,DawnA;Kuchel,GeorgeA;Yan,Riqiang;Hu,Xiangyou;Smith,PhillipP
虽然大多数阿尔茨海默病（AD）研究强调认知和行为异常，但在三分之一的AD患者中观察到下尿路症状（LUTS），导致发病率，生活质量差，需要住院治疗。阿尔茨海默病相关的泌尿功能障碍（ADUD）被认为是由于认知能力下降。虽然小鼠研究表明AD模型中膀胱神经支配和排尿行为可能会改变，但技术挑战排除了排尿反射评估。本研究旨在建立一种ADUD小鼠模型，并试图描述与AD病理学相关的排尿反射改变所涉及的非认知后遗症。我们现在提供的证据表明，在AD的转基因淀粉样变性小鼠模型中，使用膀胱测压和组织化学方法，药肌学Tg‐APP/PS1 DE 9（PA）小鼠及其野生型（WT）同窝仔（每组n= 6-8）在PA小鼠中的斑块发作之前使用（4-6个月）和PA小鼠中斑块累积后（8-10个月）相比，他们的WT对照litmates.ResultsNovel发现包括数据提示括约肌失调，与药理学证据改变肾上腺素能机制.这些数据突出了解决AD的非认知后遗症的重要性，并提供了对AD对LUTS和失禁的衰弱影响的新的翻译见解。
AimsWhile most Alzheimer's disease (AD) research emphasizes cognitive and behavioral abnormalities, lower urinary tract symptoms (LUTS) are observed in a third of AD patients, contributing to morbidity, poor quality of life, and need for institutionalization. Alzheimer's disease‐associated urinary dysfunction (ADUD) has been assumed to be due to cognitive decline alone. While mouse studies have suggested that bladder innervation and voiding behavior may be altered in AD models, technical challenges precluded voiding reflex assessments. This study seeks to establish a mouse model of ADUD, and it seeks to characterize the noncognitive sequelae involved in AD‐pathology associated alterations in the voiding reflex.MethodsHaving developed techniques permitting the assessment of bladder volume, pressure, and flow in mice, we now provide evidence of alterations in involuntary bladder control and increased response heterogeneity in a transgenic amyloidosis mouse model of AD using cystometry and tissue pharmacomyography. Tg‐APP/PS1DE9 (PA) mice and their wild‐type (WT) littermates (n= 6–8 per group) were used before plaque onset in the PA mice (4–6 months) and after plaque accumulation in the PA mice (8–10 months) in comparison to their WT control littermates.ResultsNovel findings include data suggestive of sphincteric discoordination, with pharmacological evidence of altered adrenergic mechanisms.ConclusionsTogether, these data highlight the importance of addressing noncognitive sequelae of AD and offer novel translational insights into the debilitating impact of AD on LUTS and incontinence.