Application and progress of urine detection in early detection of Alzheimer's disease

Yashang WEI, Ben J. Gu

Chinese Journal of Alzheimer's Disease and Related Disorders ›› 2025, Vol. 8 ›› Issue (1) : 47-53.

PDF(817 KB)
Home Journals Chinese Journal of Alzheimer's Disease and Related Disorders
Chinese Journal of Alzheimer's Disease and Related Disorders

Abbreviation (ISO4): Chinese Journal of Alzheimer's Disease and Related Disorders      Editor in chief: Jun WANG

About  /  Aim & scope  /  Editorial board  /  Indexed  /  Contact  / 
PDF(817 KB)
Chinese Journal of Alzheimer's Disease and Related Disorders ›› 2025, Vol. 8 ›› Issue (1) : 47-53. DOI: 10.3969/j.issn.2096-5516.2025.01.007

Application and progress of urine detection in early detection of Alzheimer's disease

Author information +
History +

Abstract

The continuous growth of Chinese economy and population, as well as the changes in social structure, have made China one of the countries with the fastest growing elderly population. The prevention and prognosis of geriatric diseases are facing great challenges. Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. The pathological characteristics of AD are the long-term (more than 20 years) deposition of neurofibrillary tangles and amyloid plaques, which lead to the death or loss of function of neurons. At present, clinical diagnosis is mainly based on cognitive tests, imaging and cerebrospinal fluid (CSF) tests, which limits the application of these diagnostic methods in the early detection of AD. Although biomarkers such as the ratio of amyloid-β (Aβ40/42) in blood and proteins such as phosphorylated Tau-181 and Tau-217 have received widespread attention, their application is usually limited to the assessment of disease progression, because changes in Tau protein are generally considered to be secondary reactions to Aβ deposition and are not suitable for early detection. Urine contains a variety of biomolecules, and its composition can reflect the physiological and pathological changes of the body in real time, which makes urine an ideal choice for biomarker discovery and early screening of diseases. The value of urine as a non-invasive peripheral metabolite biological fluid in the early detection of AD is gradually being promoted and applied. This article mainly summarizes and prospects the research progress in developing urine biomarkers as a means of early detection of AD.

Key words

Alzheimer's disease / Urine / Biomarkers / Early detection

Cite this article

Download Citations
Yashang WEI , Ben J. Gu. Application and progress of urine detection in early detection of Alzheimer's disease[J]. Chinese Journal of Alzheimer's Disease and Related Disorders. 2025, 8(1): 47-53 https://doi.org/10.3969/j.issn.2096-5516.2025.01.007

References

[1]
Rostagno AA. Pathogenesis of Alzheimer's disease[J]. Int J Mol Sci, 2022, 24(1).
[2]
Elhage A, Cohen S, Cummings J, et al. Defining benefit: clinically and biologically meaningful outcomes in the next-generation Alzheimer's disease clinical care pathway[J]. Alzheimers Dement, 2024.
[3]
Stockmann J, Verberk IMW, Timmesfeld N, et al. Amyloid-β misfolding as a plasma biomarker indicates risk for future clinical Alzheimer's disease in individuals with subjective cognitive decline[J]. Alzheimers Res Ther, 2020, 12(1): 169.
[4]
Sancesario G, Bernardini S. AD biomarker discovery in CSF and in alternative matrices[J]. Clin Biochem, 2019, 72: 52-57.
[5]
Buccellato FR, D' Anca M, Fenoglio C, et al. Role of oxidative damage in Alzheimer's disease and neurodegeneration: from pathogenic mechanisms to biomarker discovery[J]. Antioxidants (Basel), 2021, 10(9).
[6]
Jia J, Wei C, Chen S, et al. The cost of Alzheimer's disease in china and re-estimation of costs worldwide[J]. Alzheimers Dement, 2018, 14(4): 483-491.
[7]
Ilic I, Jakovljevic V, Zivanovic macuzic I, et al. Trends in global burden of Alzheimer's disease and other dementias attributable to high fasting plasma glucose, 1990-2021[J]. Medicina (Kaunas), 2024, 60(11).
[8]
Global, regional, and national burden of stroke and its risk factors, 1990-2021: a systematic analysis for the global burden of disease study 2021[J]. Lancet Neurol, 2024, 23(10): 973-1003.
[9]
Li DD, Zheng CQ, Zhang F, et al. Potential neuroprotection by dendrobium nobile lindl alkaloid in Alzheimer's disease models[J]. Neural Regen Res, 2022, 17(5): 972-977.
[10]
Hazzan AA, Dauenhauer J, Follansbee P, et al. Family caregiver quality of life and the care provided to older people living with dementia: qualitative analyses of caregiver interviews[J]. BMC Geriatr, 2022, 22(1): 86.
[11]
WAng C, Xu T, Yu W, et al. Early diagnosis of Alzheimer's disease and mild cognitive impairment based on electroencephalography: From the perspective of event related potentials and deep learning[J]. Int J Psychophysiol, 2022, 182: 182-189.
[12]
Valverde-salazar V, Ruiz-gabarre D, García-escudero V, et al. Alzheimer's disease and green tea: epigallocatechin-3-gallate as a modulator of inflammation and oxidative stress[J]. Antioxidants (Basel), 2023, 12(7).
[13]
Zhou B, Fukushima M. Clinical utility of the pathogenesis-related proteins in Alzheimer's disease[J]. Int J Mol Sci, 2020, 21(22).
[14]
Whiteaker P, George AA. Discoveries and future significance of research into amyloid-beta/α7-containing nicotinic acetylcholine receptor (nAChR) interactions[J]. Pharmacol Res, 2023, 191: 106743.
[15]
Strozyk D, Blennow K, White LR, et al. CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study[J]. Neurology, 2003, 60(4): 652-656.
[16]
Yarns BC, Holiday KA, Carlson DM, et al. Pathophysiology of Alzheimer's disease[J]. Psychiatr Clin North Am, 2022, 45(4): 663-676.
[17]
Zhou R, Ji B, Kong Y, et al. PET imaging of neuroinflammation in Alzheimer's disease[J]. Front Immunol, 2021, 12: 739130.
[18]
Weiner MW, Kanoria S, Miller MJ, et al. Overview of Alzheimer's disease neuroimaging initiative and future clinical trials[J]. Alzheimers Dement, 2024.
[19]
Iulita MF, Bejanin A, Vilaplana E, et al. Association of biological sex with clinical outcomes and biomarkers of Alzheimer's disease in adults with down syndrome[J]. Brain Commun, 2023, 5(2): fcad074.
[20]
Karaboğa MNS, Sezgintürk MK. Biosensor approaches on the diagnosis of neurodegenerative diseases: sensing the past to the future[J]. J Pharm Biomed Anal, 2022, 209: 114479.
[21]
Martinez B, Peplow PV. MicroRNA biomarkers in frontotemporal dementia and to distinguish from Alzheimer's disease and amyotrophic lateral sclerosis[J]. Neural Regen Res, 2022, 17(7): 1412-22.
[22]
Song S, Lee JU, Jeon MJ, et al. Detection of multiplex exosomal miRNAs for clinically accurate diagnosis of Alzheimer's disease using label-free plasmonic biosensor based on DNA-Assembled advanced plasmonic architecture[J]. Biosens Bioelectron, 2022, 199: 113864.
[23]
Cortés Malagón EM, López ornelas A, Olvera Gómezi, et al. The kynurenine pathway, aryl hydrocarbon receptor, and Alzheimer's disease[J]. Brain Sci, 2024, 14(9).
[24]
Ghiso J, Calero M, Matsubara E, et al. Alzheimer's soluble amyloid beta is a normal component of human urine[J]. FEBS Lett, 1997, 408(1): 105-108.
[25]
Takata M, Nakashima M, Takehara T, et al. Detection of amyloid beta protein in the urine of Alzheimer's disease patients and healthy individuals[J]. Neurosci Lett, 2008, 435(2): 126-130.
[26]
Wongta A, Hongsibsong S, Chantara S, et al. Development of an immunoassay for the detection of amyloid beta 1-42 and its application in urine samples[J]. J Immunol Res, 2020, 2020: 8821181.
[27]
Balhara N, Devi M, Balda A, et al. Urine; a new promising biological fluid to act as a non-invasive biomarker for different human diseases[J]. 2023, 5.
[28]
Zhang C, Nestorova G, Rissman RA, et al. Detection and quantification of 8-hydroxy-2'-deoxyguanosine in Alzheimer's transgenic mouse urine using capillary electrophoresis[J]. Electrophoresis, 2013, 34(15): 2268-2274.
[29]
Lee KH, Cha M, Lee BH, et al. Neuroprotective effect of antioxidants in the brain[J]. 2020, 21(19): 7152.
[30]
Lee SH, Kim I, Chung BC, et al. Increased urinary level of oxidized nucleosides in patients with mild-to-moderate Alzheimer's disease[J]. Clin Biochem, 2007, 40(13-14): 936-938.
[31]
Bou-nader C, Stull FW, Pecqueur L, et al. An enzymatic activation of formaldehyde for nucleotide methylation[J]. Nature Communications, 2021, 12(1): 4542.
[32]
Yiduo K, Hang Z, Dehua C, et al. Formaldehyde toxicity in age-related neurological dementia[J]. Ageing Res Rev, 2021, 73: 101512.
[33]
Wang Y, Wang Y, Zhu J, et al. Systematic evaluation of urinary formic acid as a new potential biomarker for Alzheimer's disease[J]. Front Aging Neurosci, 2022, 14: 1046066.
[34]
Chen F, Wang N, Tian X, et al. The potential diagnostic accuracy of urine formaldehyde levels in Alzheimer's disease: a systematic review and meta-analysis[J]. Front Aging Neurosci, 2022, 14: 1057059.
[35]
Tong Z, Wang W, Luo W, et al. Urine formaldehyde predicts cognitive impairment in post-stroke dementia and Alzheimer's disease[J]. J Alzheimers Dis, 2017, 55(3): 1031-1038.
[36]
Wang Y, Pan F, Xie F, et al. Correlation between urine formaldehyde and cognitive abilities in the clinical spectrum of Alzheimer's disease[J]. Front Aging Neurosci, 2022, 14: 820385.
[37]
Monte SM, Ghanbari K, Frey WH, et al. Characterization of the AD7C-NTP cDNA expression in Alzheimer's disease and measurement of a 41-kD protein in cerebrospinal fluid[J]. J Clin Invest, 1997, 100(12): 3093-3104.
[38]
Butcher J. Urine tests for Alzheimer's disease--are they fool's gold?[J]. Lancet Neurol, 2007, 6(2): 106-107.
[39]
Li Y, Kang M, Wang H, et al. Urinary Alzheimer-associated neuronal thread protein is not elevated in patients with subjective cognitive decline and patients with depressive state[J]. J Alzheimers Dis, 2019, 71(4): 1115-1123.
[40]
Zhang J, Zhang CH, Li RJ, et al. Accuracy of urinary AD7c-NTP for diagnosing Alzheimer's disease: a systematic review and meta-analysis[J]. J Alzheimers Dis, 2014, 40(1): 153-159.
[41]
Zhang N, Zhang L, Li Y, et al. Urine AD7c-NTP predicts amyloid deposition and symptom of agitation in patients with Alzheimer's disease and mild cognitive impairment[J]. J Alzheimers Dis, 2017, 60(1): 87-95.
[42]
Giammanco A, Spina R, Cefalù AB, et al. APOC-III: a gatekeeper in controlling triglyceride metabolism[J]. Curr Atheroscler Rep, 2023, 25(3): 67-76.
[43]
Zhang X. Higher plasma APOC-III was associated with a slower reduction of β-amyloid levels in cerebrospinal fluid among older individuals without dementia[J]. Neuropsychiatr Dis Treat, 2020, 16: 1139-1144.
[44]
Watanabe Y, HIrao Y, Kasuga K, et al. Urinary apolipoprotein C3 is a potential biomarker for Alzheimer's disease[J]. Dement Geriatr Cogn Dis Extra, 2020, 10(3): 94-104.
[45]
Lepara O, Zaciragic A, Fajkic A, et al. Peripheral 8-iso-PGF2α as a biomarker in bosnian patients with Alzheimer's disease and vascular dementia[J]. Psychiatr Danub, 2020, 32(3-4): 389-394.
[46]
Huang X. A concise review on oxidative stress-mediated ferroptosis and cuproptosis in Alzheimer's disease[J]. Cells, 2023, 12(10).
[47]
Ionescu-tucker A, Cotman CW. Emerging roles of oxidative stress in brain aging and Alzheimer's disease[J]. Neurobiol Aging, 2021, 107: 86-95.
[48]
Barreiro K, Huber TB, Holthofer H, et al. Isolating urinary extracellular vesicles as biomarkers for diabetic disease[J]. Methods Mol Biol, 2020, 2067: 175-188.
[49]
Chan HN, Xu D, Ho SL, et al. Ultra-sensitive detection of protein biomarkers for diagnosis of Alzheimer's disease[J]. Chem Sci, 2017, 8(5): 4012-4018.
[50]
Watanabe Y, Hirao Y, Kasuga K, et al. Molecular network analysis of the urinary proteome of Alzheimer's disease patients[J]. Dement Geriatr Cogn Dis Extra, 2019, 9(1): 53-65.
[51]
Hajjri SN, Sadigh-eteghad S, Mehrpour M, et al. Beta-Amyloid-Dependent miRNAs as circulating biomarkers in Alzheimer's disease: a preliminary report[J]. J Mol Neurosci, 2020, 70(6): 871-877.
[52]
Wiedrick JT, Phillips JI, Lusardi TA, et al. Validation of MicroRNA biomarkers for Alzheimer's disease in human cerebrospinal fluid[J]. J Alzheimers Dis, 2019, 67(3): 875-891.
[53]
Nam D, Lee JY, Lee M, et al. Detection and assessment of α-synuclein oligomers in the urine of parkinson's disease patients[J]. J Parkinsons Dis, 2020, 10(3): 981-991.
[54]
Song X, Chen Z, Zheng Y, et al. Urine proteomics in cardiovascular disease: advances in biomarker discovery and clinical applications[J]. Expert Rev Proteomics, 2024: 1-15.
[55]
Sun R, Wang H, Shi Y, et al. A pilot study of urinary exosomes in Alzheimer's disease[J]. Neurodegener Dis, 2019, 19(5-6): 184-191.
[56]
Rotter M, Brandmaier S, Prehn C, et al. Stability of targeted metabolite profiles of urine samples under different storage conditions[J]. Metabolomics, 2017, 13(1): 4.
[57]
Li W, Kui L, Demetrios T, et al. A glimmer of hope: maintain mitochondrial homeostasis to mitigate Alzheimer's disease[J]. Aging Dis, 2020, 11(5): 1260-1275.
[58]
Lee JH, Yang DS, Goulbourne CN, et al. Faulty autolysosome acidification in Alzheimer's disease mouse models induces autophagic build-up of Aβ in neurons, yielding senile plaques[J]. Nat Neurosci, 2022, 25(6): 688-701.
[59]
Armenta-castro A, Núñez-soto MT, Rodriguez-aguillón KO, et al. Urine biomarkers for Alzheimer's disease: a new opportunity for wastewater-based epidemiology?[J]. Environ Int, 2024, 184: 108462.

Footnotes

PDF(817 KB)

Accesses

Citation

Detail

Sections
Recommended

/