Alzheimer's disease amyloidogenesis is linked to altered lower urinary tract physiology.
Alzheimer's disease
Alzheimer's disease-associated urinary dysfunction
amyloidosis
cystometry
pharmacomyography
Journal
Neurourology and urodynamics
ISSN: 1520-6777
Titre abrégé: Neurourol Urodyn
Pays: United States
ID NLM: 8303326
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
04
04
2022
received:
01
03
2022
accepted:
14
04
2022
pubmed:
18
5
2022
medline:
28
7
2022
entrez:
17
5
2022
Statut:
ppublish
Résumé
While 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. Having 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. Novel findings include data suggestive of sphincteric discoordination, with pharmacological evidence of altered adrenergic mechanisms. Together, 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.
Substances chimiques
Amyloid beta-Protein Precursor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1344-1354Subventions
Organisme : NINDS NIH HHS
ID : RF1 NS074256
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG058814
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG061609
Pays : United States
Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
Lee SH, Cho ST, Na HR, Ko SB, Park MH. Urinary incontinence in patients with Alzheimer's disease: relationship between symptom status and urodynamic diagnoses. Int J Urol. 2014;21(7):683-687.
Risacher SL, McDonald BC, Tallman EF, et al. Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults. JAMA Neurol. 2016;73(6):721-732.
Woodford HJ, Stevenson JM. Anticholinergic drugs and dementia: time for transparency in the face of uncertainty. Cochrane Database Syst Rev. 2021;9:ED000154.
Centers for Medicare & Medicaid Services (U.S.). Prevalence of incontinence among older Americans. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics; 2014.
Jung HB, Choi DK, Lee SH, Cho ST, Na HR, Park MH. Correlation between overactive bladder symptom score and neuropsychological parameters in Alzheimer's disease patients with lower urinary tract symptom. Int Braz J Urol. 2017;43(2):256-263.
Polanco JC, Li C, Bodea LG, Martinez-Marmol R, Meunier FA, Gotz J. Amyloid-beta and tau complexity-towards improved biomarkers and targeted therapies. Nat Rev Neurol. 2018;14(1):22-39.
Gotz J, Bodea LG, Goedert M. Rodent models for Alzheimer disease. Nat Rev Neurosci. 2018;19(10):583-598.
Jankowsky JL, Fadale DJ, Anderson J, et al. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet. 2004;13(2):159-170.
Biallosterski BT, de Wachter SG, van Koeveringe GA, et al. Changes in bladder innervation in a mouse model of Alzheimer's disease. J Chem Neuroanat. 2010;39(3):204-210.
Biallosterski BT, Prickaerts J, Rahnama'i MS, de Wachter S, van Koeveringe GA, Meriaux C. Changes in voiding behavior in a mouse model of Alzheimer's disease. Front Aging Neurosci. 2015;7:160.
Gupta S, Goyal P, Idrees S, Aggarwal S, Bajaj D, Mattana J. Association of endocrine conditions with Takotsubo cardiomyopathy: a comprehensive review. J Am Heart Assoc. 2018;7(19):e009003.
Hardy CC, Keilich SR, Harrison AG, Knight BE, Baker DS, Smith PP. The aging bladder phenotype is not the direct consequence of bladder aging. Neurourol Urodyn. 2019;38(8):2121-2129.
Smith PP, DeAngelis A, Kuchel GA. Detrusor expulsive strength is preserved, but responsiveness to bladder filling and urinary sensitivity is diminished in the aging mouse. Am J Physiol Regul Integr Comp Physiol. 2012;302(5):R577-R586.
Smith PP, DeAngelis A, Simon R. Evidence of increased centrally enhanced bladder compliance with ageing in a mouse model. BJU Int. 2015;115(2):322-329.
Smith PP, Deangelis AM, Kuchel GA. Evidence of central modulation of bladder compliance during filling phase. Neurourol Urodyn. 2012;31(1):30-35.
Werner ME, Knorn AM, Meredith AL, Aldrich RW, Nelson MT. Frequency encoding of cholinergic- and purinergic-mediated signaling to mouse urinary bladder smooth muscle: modulation by BK channels. Am J Physiol: Regul, Integr Comp Physiol. 2007;292(1):R616-R624.
Langdale CL, Grill WM. Phasic activation of the external urethral sphincter increases voiding efficiency in the rat and the cat. Exp Neurol. 2016;285(pt B):173-181.
Ferrara N, Komici K, Corbi G, et al. Beta-adrenergic receptor responsiveness in aging heart and clinical implications. Front Physiol. 2014;4:396.
Luong K, Nguyen LT. The role of beta-adrenergic receptor blockers in Alzheimer's disease: potential genetic and cellular signaling mechanisms. Am J Alzheimers Dis Other Demen. 2013;28(5):427-439.
Hampel H, Mesulam MM, Cuello AC, et al. The cholinergic system in the pathophysiology and treatment of Alzheimer's disease. Brain. 2018;141(7):1917-1933.
Masuda H, Chancellor MB, Kihara K, et al. Effects of cholinesterase inhibition in supraspinal and spinal neural pathways on the micturition reflex in rats. BJU Int. 2009;104(8):1163-1169.
Takahashi O, Sakakibara R, Panicker J, et al. White matter lesions or Alzheimer's disease: which contributes more to overactive bladder and incontinence in elderly adults with dementia? J Am Geriatr Soc. 2012;60(12):2370-2371.
Hou Y, Dan X, Babbar M, et al. Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol. 2019;15(10):565-581.
Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 2016;8(6):595-608.
Selkoe DJ. Alzheimer's disease results from the cerebral accumulation and cytotoxicity of amyloid beta-protein. J Alzheimers Dis. 2001;3(1):75-80.
Heneka MT, Kummer MP, Stutz A, et al. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature. 2013;493(7434):674-678.
Barnat M, Capizzi M, Aparicio E, et al. Huntington's disease alters human neurodevelopment. Science. 2020;369(6505):787-793.