Clinical relevance of plasma ADAM-17 with cognition and neurodegeneration in Alzheimer's disease

Abstract

Background

A disintegrin and metalloproteinase 17 (ADAM-17) has multiple pathophysiological functions in Alzheimer's disease (AD). However, the clinical relevance of ADAM-17 in AD is not clear yet.

Objective

This study aims to investigate the levels of circulating ADAM-17 and their association with AD.

Methods

This cross-sectional study recruited 40 normal cognition (NC) participants and 36 AD patients. Plasma ADAM-17 and biomarkers of neurodegeneration were determined. The association of plasma ADAM-17 with cognitive functions and biomarkers of neurodegeneration was analyzed.

Results

Plasma ADAM-17 levels were elevated in AD patients in comparison with NC subjects. Plasma ADAM-17 was positively associated with Clinical Dementia Rating (CDR) scores, but negatively associated with the Mini-Mental State Examination scores and Montreal Cognitive Assessment scores. Plasma ADAM-17 levels were positively associated with the levels of Aβ₄₀, Aβ₄₂, and p-Tau181.

Conclusions

These findings suggest a link between ADAM-17 and the pathogenesis of AD from a clinical perspective.

Keywords

ADAM-17 Alzheimer's disease amyloid-β cognitive impairment tau

Introduction

Alzheimer's disease (AD) is currently the seventh leading cause of death worldwide and one of the main causes of disability and inability among older adults.^1,2 The main pathological hallmarks of AD include extracellular senile plaque composed of amyloid-β (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein.³

As an α-secretase enzyme of amyloid-β protein precursor, a disintegrin and metalloprotease 17 (ADAM-17) can compete with β-secretase, which could cleave Aβ precursor protein to generate Aβ,^4–10 thus promoting the nonamyloidogenic pathway. Furthermore, loss-of-function mutation of ADAM-17 is associated with the onset of familial AD, suggesting a protective role of ADAM-17 in the AD brain.¹¹ However, ADAM-17 is also involved in inflammatory pathways in the brain.^12–15 Therefore, ADAM-17 has complex pathophysiological functions in the brain.

Currently, there is no research on the clinical relevance of ADAM-17 in AD patients. Therefore, this study aimed to investigate the association between ADAM-17 and AD clinical severity and biomarkers of neurodegeneration. We examined the levels of ADAM-17 in AD patients and explored their association with clinical severity of AD and biomarkers of neurodegeneration.

Methods

Study population

This study recruited individuals with cognitive complaints who visited the memory clinic at the Department of Neurology, Daping Hospital between January 2022 and December 2022. Subjects with normal cognition were recruited from the Health Examination Center from the same hospital during the same period. A total of 40 subjects with normal cognition (NC) and 36 subjects diagnosed with AD were included in this study. The inclusion criteria included: (1) willingness to participate; (2) NC subjects should have no memory complaints and tested normal in cognitive assessment; (3) AD subjects should have cognitive impairment in cognitive screening. The exclusion criteria included: (1) had a coexisting disorder that may affect cognition, such as schizophrenia, infections of the central nervous system, Parkinson's disease, and autoimmune encephalitis; (3) had any type of tumor; (4) had a systemic inflammatory disease, chronic infectious disease, or acute infection during the past 4 weeks; (5) declined to participate or blood sampling. Written informed consent for participation and blood sampling was obtained from all participants or their legal guardians. The research protocol fulfills the criteria of the Ethics committee of Daping Hospital, Third Military Medical University.

Clinical assessments and diagnosis of AD

All participants of the study were recruited from a single cohort, the China Aging and Dementia Study (CADS) from the Daping Hospital, Chongqing, China. The CADS cohort was established as a research platform, following the 2011 National Institute on Aging and Alzheimer's Association (NIA-AA) recommended Aβ deposition pathologic tau, and neurodegeneration (ATN) research framework,^16,17 to characterize neurodegeneration-related cognitive impairment diseases and NC individuals. The general cognitive functions were examined with the Mini-Mental State Examination (MMSE). Subjects with an MMSE score below 27 were further subjected to a battery of neuropsychological tests, including the Clinical Dementia Rating (CDR), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL), Hachinski Ischemic Scale (HIS), and Boston Naming Test.^18–22 CDR was used to judge cognitively normal (CDR = 0), MCI (CDR = 0.5), and dementia (CDR ≥ 1). About 1/3 of all subjects with a CDR of 0.5 or above underwent an MRI scan, an Aβ-amyloid PET scan using ¹¹C Pittsburgh Compound B (PiB) tracer, and an FDG-PET scan to confirm the cause of cognitive decline. Additionally, AD participants received apolipoprotein E (APOE) genotyping according to the established protocol in our laboratory.^23,24

Measurements of plasma ADAM-17, Aβ₄₀, Aβ₄₂, t-Tau, and p-Tau181

Fasting blood was collected from all participants between 07:00 and 08:00 am. The blood samples were centrifuged within one hour after collection, and the ethylenediamine tetraacetic acid (EDTA) plasma was equally divided into 0.5 mL polypropylene test tubes and stored at −80°C until use. Written informed consent was obtained from all participants and their legal guardians before blood samples were collected.

After collecting the plasma samples from all participants, a human ADAM-17 combined with an immunosorbent assay (ELISA) kit (Jingbai Biology Co., Ltd, Hangzhou, China) was used to determine the levels of ADAM-17 in plasma. Plasma levels of Aβ₄₀, Aβ_42, and t-Tau were measured by the commercially available single molecular array (SIMOA) human neurological 3-Plex A test kit (Quanterix, USA) using automated SIMOA HD-1Z analyzer (Quanterix, USA). Plasma levels of p-Tau181 were measured by the commercially available SIMOA human p-Tau181 test kit (Quanterix, USA) using an automated SIMOA HD-1Z analyzer (Quanterix, USA).

Statistical analysis

For each plasma cytokine, the normality distribution was checked using the Shapiro-Wilk test. Since ADAM-17 levels did not exhibit a normal distribution, they were natural logarithmic (ln) transformed for analysis. Continuous variables were described as means ± standard deviations (SD) or median (IQR) where appropriate, while classified data were summarized as numbers and frequencies. The frequency differences of gender and APOE ε4 were evaluated by chi-square test. Differences in other demographic characteristics and ADAM-17 levels were tested by a two-sample independent t-test (or students’ t-test and Welch's correction if the F test showed significant differences between groups). We used partial correlation analysis to adjust for age, sex, and education levels when analyzing the correlation between ADAM-17 levels and Aβ and tau levels. The computations were performed with SPSS version 20.0 (SPSS Inc., United States).

Results

Characteristics of participants

The characteristics of the participants are shown in Table 1. There was no difference in age, sex, education level or frequencies of diabetes mellitus, hypertension, and cardiovascular disease between the AD group and the NC group. As expected, the mean MMSE scores of the AD dementia group were significantly lower than those of the NC group (Table 1).

Table 1.

The characteristics of all participants.

Variables	NC (N = 40)	AD (N = 36)	p
Age, mean ± SD, y	71.73 ± 7.61	67.74 ± 10.06	0.063
Female, number (%)	24 (60.0)	23 (63.9)	0.803
Education, mean ± SD, y	7.75 ± 4.82	9.26 ± 3.35	0.109
MMSE, mean ± SD	27.03 ± 2.09	15.00 ± 7.35	<0.001
Diabetes, number (%)	8 (21.1)	8 (21.6)	0.745
Hypertension, number (%)	20 (50.0)	15 (41.7)	0.835
Coronary artery disease, number (%)	12 (30.0)	5 (13.9)	0.103
History of stroke, number (%)	5 (12.5)	2 (5.6)	0.510
Plasma Aβ₄₀, ng/mL	263.31 ± 47.43	243.02 ± 71.48	0.210
Plasma Aβ₄₂, ng/mL	10.78 ± 2.56	9.68 ± 2.94	0.143
Plasma t-Tau, ng/mL	3.58 ± 1.50	4.76 ± 1.27	<0.0001
Plasma p-Tau181, ng/mL	2.05 ± 1.17	4.76 ± 1.27	<0.0001

NC: normal cognition; AD: Alzheimer's disease; MMSE: Mini-Mental State Examination; APOE: apolipoprotein E; SD: standard deviation.

Plasma ADAM-17 is upregulated in AD patients

The overall levels of plasma ADAM-17 levels in AD subjects were higher than those in NC subjects (mean ± SD: 467.6 ± 682.8 versus 222.2 ± 184.7 pg/ml, p = 0.032; Figure 1(a)). Furthermore, the difference was even more significant between the APOE ε4 (+) AD patients and NC subjects (mean ± SD: 668.0 ± 833.8 versus 225.9 ± 191.7 pg/ml, p = 0.003; Figure 1(b)). After logarithmic transformed, levels of plasma ADAM-17 levels in AD subjects and NC subjects have no significant difference (mean ± SD: 5.543 ± 0.967 versus 5.220 ± 0.534 pg/ml, p = 0.072; Figure 1(c)), but the difference was significant between the APOE ε4 (+) AD patients and NC subjects (mean ± SD: 5.895 ± 1.088 versus 5.224 ± 0.555, p = 0.003; Figure 1(d)), and between the APOE ε4 (+) AD patients and the APOE ε4 (-) AD patients (mean ± SD: 5.895 ± 1.088 versus 5.151 ± 0.636, p = 0.019; Figure 1(d)).

Figure 1.

Comparison of plasma ADAM-17 levels and ln (plasma ADAM-17 levels) between different groups. (a) Comparison of plasma ADAM-17 levels between NC subjects and AD patients. (b) Comparison of plasma ADAM-17 levels between NC subjects, APOE ε4 (+) AD patients and APOE ε4 (-) AD patients. (c) Comparison of ln (plasma ADAM-17) between NC subjects and AD patients. (d) Comparison of ln (plasma ADAM-17) between NC subjects, APOE ε4 (+) AD patients and APOE ε4 (-) AD patients. ADAM-17: A disintegrin and metalloprotease 17; NC: normal cognition; AD: Alzheimer's disease; APOE: apolipoprotein E.

Plasma ADAM-17 is associated with the AD biomarkers

In AD patients, plasma ADAM-17 levels were positively correlated with Aβ₄₀ (γ = 0.331, p = 0.049; Figure 2(a)), Aβ₄₂ (γ = 0.359, p = 0.032; Figure 2(b)), and p-Tau181 levels (γ = 0.377, p = 0.024; Figure 2(e)). In NC subjects, there was no correlation between ADAM-17 levels and Aβ₄₀ (γ = −0.040, p = 0.808; Figure 2(a)), Aβ₄₂ (γ = 0.077, p = 0.636; Figure 2(b)), or p-Tau181 levels (γ = 0.022, p = 0.893; Figure 2(e)). Among NC subjects and AD patients, plasma ADAM-17 levels were not correlated with Aβ_42/40 (Figure 2(c)) and t-Tau levels (Figure 2(d)).

Figure 2.

Correlation analysis between plasma ADAM-17 and plasma aβ, tau levels. (a) Correlation between ADAM-17 levels and Aβ₄₀ levels. (b) Correlation between ADAM-17 levels and Aβ₄₂ levels. (c) Correlation between ADAM-17 levels and Aβ_42/40. (d) Correlation between ADAM-17 levels and t-Tau levels. (e) Correlation between ADAM-17 levels and p-Tau181 levels. ADAM-17: A disintegrin and metalloprotease 17; Aβ: amyloid-β; AD: Alzheimer's disease; NC: normal cognition.

Plasma ADAM-17 is associated with cognitive functions

In AD patients, plasma ADAM-17 levels were negatively correlated with MMSE scores (γ = −0.343, p = 0.040; Figure 3(a)) and MoCA scores (γ = −3651, p = 0.0285; Figure 3(b)), and positively correlated with CDR scores (γ = 0.4928, p = 0.0026; Figure 3(c)), but no correlation with ADL scores, HIS scores and Boston Naming Test scores. In NC subjects, there was no correlation between ADAM-17 levels and MMSE scores (γ = 0.057, p = 0.727; Figure 3(a)).

Figure 3.

Correlation analysis between plasma ADAM-17 and cognitive function scores. (a) Correlation between ADAM-17 levels and MMSE scores. (b) Correlation between ADAM-17 levels and MoCA scores. (c) Correlation between ADAM-17 levels and CDR scores. (d) Correlation between ADAM-17 levels and HIS scores. (e) Correlation between ADAM-17 levels and Boston Naming Test scores. (f) Correlation between ADAM-17 levels and ADL scores. ADAM-17: A disintegrin and metalloprotease 17; AD: Alzheimer's disease; NC: normal cognition; TG: Total group; MMSE: Mini-Mental State Examination; MoCA: Montreal Cognitive Assessment; CDR: Clinical Dementia Rating; HIS: Hachinski Ischemic Scale; ADL: Activities of Daily Living.

Discussion

In this cross-sectional study, we investigated the clinical relevance of plasma ADAM-17 in AD in a Chinese cohort. Briefly, we found that plasma ADAM-17 is upregulated in AD patients. Furthermore, plasma ADAM-17 is associated with the severity of cognitive impairment and biomarkers of neurodegeneration.

The circulating levels of ADAM-17 have rarely been investigated in AD. A previous study reported that cerebrospinal fluid ADAM-17 activities are upregulated in AD patients.²⁵ Another study found upregulated activities of ADAM-17 in plasma in patients with mild cognitive impairment and AD dementia.²⁶ Consistently, a study conducted in the Chinese population also identified increased ADAM-17 activities in AD patients,²⁷ which is in accordance with our present findings. The upregulation of ADAM-17 as a consequence of AD or an initiation event in AD is not clear yet.

As an α-secretase, ADAM-17 has a physical protective role in the brain by inhibiting the production of Aβ.^5,6,9,10 Consistently, a rare loss-of-function variant in ADAM-17 is linked to an increased risk of developing AD,¹¹ suggesting the complete loss of function of ADAM-17 is pathogenic in AD. However, there has been increasing evidence pointing to the opposite conclusion that ADAMs targeting cytokines and chemokines can actually cause inflammatory processes, and consequently neurodegeneration.^12–15 Therefore, there are two possible mechanisms underlying the increase in ADAM-17 in AD patients. The first possibility is that the increase in this α-secretase is a consequence of AD, serving as an adaptive response to resist the accumulation of Aβ in the brain. The second possibility is that the increase in ADAM-17 is an upstream event of AD that contributes to the formation of the inflammatory environment in the brain. However, we could address this issue based on the current findings.

In the present study, we discovered that plasma ADAM-17 is associated with biomarkers of neurodegeneration, such as Aβ₄₂, Aβ₄₀, and p-Tau181. These biomarkers reflect brain amyloidosis and the severity of neuronal injury with high accuracy.^28–30 Therefore, we believe that ADAM-17 might be a reliable indicator of brain neurodegeneration in AD patients. This notion is supported by the finding that APOE ε4 carriers had higher levels of ADAM-17 than noncarriers, with the general understanding that APOE ε4 carriers typically exhibit a higher burden of amyloid in the brain compared to noncarriers.³¹ Previous research has shown that APOE ε4 gene promotes abnormalities in microglia, causing neurotoxic microglia-derived factor TNF-α.³² The hydrolysis product sTNFR of the latter correlated strongly with ADAM-17 activity in AD subjects.²⁵ Furthermore, ADAM-17 could cleave TNFR2 signaling pathway,³³ which is a neuroprotective pathway.³⁴ So it is a reasonable supposition that APOE ε4 promotes the expression of TNF-α, thus increasing ADAM-17. Afterwards, they both promote neuroinflammation, tau phosphorylation and Aβ production.

This study has several limitations that should be noted. Firstly, the small sample size and cross-sectional nature may restrict the evaluation of its findings. Longitudinal cohort studies would be beneficial for establishing a causative relationship between ADAM-17 upregulation and the development of AD from a clinical perspective. Mechanistic studies are also necessary to address this issue. Secondly, we did not investigate the changes in ADAM-17 along the AD continuum, which is crucial for understanding the role of ADAM-17 in the progression of the disease. Thirdly, the proportion of APOE ε4 carriers among the healthy controls is not clearly specified, which leads to our lack of comprehensive research on APOE, and inability to be adjusted by APOE genotype. This issue needs to be further investigated in the future. Lastly, the correlation between circulating levels of ADAM-17 and its levels in the brain remains undetermined. Therefore, it is imperative to measure the levels of ADAM-17 in the cerebrospinal fluid as they may provide a more accurate reflection of the brain environment. However, this study provides valuable clinical evidence that supplements the findings of the increased activities of ADAM-17 in AD.

Footnotes

Acknowledgments

The authors have no acknowledgments to report.

ORCID iDs

Zu-Qi Chen

Meng-Ting Wang

Cheng-Rong Tan

Shan Huang

Fa-Ying Zhou

Ying-Ying Shen

Gui-Hua Zeng

Dong-Yu Fan

Yan-Jiang Wang

Author contributions

Zu-Qi Chen (Conceptualization; Data curation; Investigation; Methodology; Resources; Software; Writing – original draft); Meng-Ting Wang (Methodology; Resources); Cheng-Rong Tan (Data curation; Resources); Shan Huang (Data curation; Resources); Fa-Ying Zhou (Data curation); Ying-Ying Shen (Data curation); Gui-Hua Zeng (Data curation); Dong-Yu Fan (Funding acquisition; Project administration; Supervision; Writing – review & editing); Yan-Jiang Wang (Funding acquisition; Project administration; Supervision; Writing – review & editing).

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the Chongqing Science and Health Project (No. 2024GGXM003 to WYJ), the Key Special Project of National Key Research and Development Programme (No. 2023YFC3605400 to WYJ), and the National Natural Science Foundation of China (No. 82201585 to FDY).

Data availability

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

References

Wang

Masters

, et al. A systemic view of Alzheimer disease – insights from amyloid-β metabolism beyond the brain. Nat Rev Neurol 2017; 13: 612–623.

Jia

Quan

, et al. Dementia in China: epidemiology, clinical management, and research advances. Lancet Neurol 2020; 19: 81–92.

Ittner

Götz

. Amyloid-β and tau–a toxic pas de deux in Alzheimer's disease. Nat Rev Neurosci 2011; 12: 65–72.

Edwards

Handsley

Pennington

. The ADAM metalloproteinases. Mol Aspects Med 2008; 29: 258–289.

Buxbaum

Liu

Luo

, et al. Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor. J Biol Chem 1998; 273: 27765–27767.

Peschon

Slack

Reddy

, et al. An essential role for ectodomain shedding in mammalian development. Science 1998; 282: 1281–1284.

Lammich

Kojro

Postina

, et al. Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease. Proc Natl Acad Sci U S A 1999; 96: 3922–3927.

Koike

Tomioka

Sorimachi

, et al. Membrane-anchored metalloprotease MDC9 has an alpha-secretase activity responsible for processing the amyloid precursor protein. Biochem J 1999; 343(Pt 2): 371–375.

Hartmann

de Strooper

Serneels

, et al. The disintegrin/metalloprotease ADAM 10 is essential for notch signalling but not for alpha-secretase activity in fibroblasts. Hum Mol Genet 2002; 11: 2615–2624.

10.

Brou

Logeat

Gupta

, et al. A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE. Mol Cell 2000; 5: 207–216.

11.

Hartl

May

, et al. A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease. Mol Psychiatry 2020; 25: 629–639.

12.

Iemmolo

Ghersi

Bivona

. The cytokine CX3CL1 and ADAMs/MMPs in concerted cross-talk influencing neurodegenerative diseases. Int J Mol Sci 2023; 24: 8026.

13.

Morganti

Nash

Grimmig

, et al. The soluble isoform of CX3CL1 is necessary for neuroprotection in a mouse model of Parkinson's disease. J Neurosci 2012; 32: 14592–14601.

14.

Nash

Moran

Finneran

, et al. Fractalkine over expression suppresses α-synuclein-mediated neurodegeneration. Mol Ther 2015; 23: 17–23.

15.

Jiang

Bhaskar

. Dynamics of the complement, cytokine, and chemokine systems in the regulation of synaptic function and dysfunction relevant to Alzheimer's disease. J Alzheimers Dis 2017; 57: 1123–1135.

16.

McKhann

Knopman

Chertkow

, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the national institute on aging-Alzheimer's association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011; 7: 263–269.

17.

Sperling

Aisen

Beckett

, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the national institute on aging-Alzheimer's association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011; 7: 280–292.

18.

Xiong

Aschenbrenner

, et al. Item response theory analysis of the clinical dementia rating. Alzheimers Dement 2021; 17: 534–542.

19.

Pinto

TCC

Machado

Bulgacov

, et al.

Is the Montreal cognitive assessment (MoCA) screening superior to the Mini-mental state examination (MMSE) in the detection of mild cognitive impairment (MCI) and Alzheimer's disease (AD) in the elderly?

Int Psychogeriatr 2019; 31: 491–504.

20.

Jia

Liu

, et al. Comprehensive management of daily living activities, behavioral and psychological symptoms, and cognitive function in patients with Alzheimer's disease: a Chinese consensus on the comprehensive management of Alzheimer's disease. Neurosci Bull 2021; 37: 1025–1038.

21.

Moroney

Bagiella

Desmond

, et al. Meta-analysis of the Hachinski ischemic score in pathologically verified dementias. Neurology 1997; 49: 1096–1105.

22.

Williams

Mack

Henderson

. Boston naming test in Alzheimer's disease. Neuropsychologia 1989; 27: 1073–1079.

23.

Fan

Jian

Huang

, et al. Establishment of combined diagnostic models of Alzheimer's disease in a Chinese cohort: the Chongqing ageing & dementia study (CADS). Transl Psychiatry 2022; 12: 252.

24.

Wang

Fan

, et al. Association of polygenic risk score with age at onset and cerebrospinal fluid biomarkers of Alzheimer's disease in a Chinese cohort. Neurosci Bull 2020; 36: 696–704.

25.

Jiang

Hampel

Prvulovic

, et al. Elevated CSF levels of TACE activity and soluble TNF receptors in subjects with mild cognitive impairment and patients with Alzheimer's disease. Mol Neurodegener 2011; 6: 69.

26.

Sun

Hampel

Blennow

, et al. Increased plasma TACE activity in subjects with mild cognitive impairment and patients with Alzheimer's disease. J Alzheimers Dis 2014; 41: 877–886.

27.

Bai

Song

, et al. Elevated plasma levels of soluble TNFRs and TACE activity in Alzheimer's disease patients of Northern Han Chinese descent. Curr Alzheimer Res 2013; 10: 57–62.

28.

Janelidze

Barthélemy

Salvadó

, et al. Plasma phosphorylated tau 217 and Aβ42/40 to predict early brain Aβ accumulation in people without cognitive impairment. JAMA Neurol 2024; 81: 947–957.

29.

Palmqvist

Tideman

Mattsson-Carlgren

, et al. Blood biomarkers to detect Alzheimer disease in primary care and secondary care. JAMA 2024; 332: 1245–1257.

30.

Barthélemy

Salvadó

Schindler

, et al. Highly accurate blood test for Alzheimer's disease is similar or superior to clinical cerebrospinal fluid tests. Nat Med 2024; 30: 1085–1095.

31.

Liu

Kanekiyo

, et al. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol 2013; 9: 106–118.

32.

Haney

Pálovics

Munson

, et al. APOE4/4 Is linked to damaging lipid droplets in Alzheimer's disease microglia. Nature 2024; 628: 154–161.

33.

Cheng

Yang

, et al. Differential activation of tumor necrosis factor receptors distinguishes between brains from Alzheimer's disease and non-demented patients. J Alzheimers Dis 2010; 19: 621–630.

34.

Shen

Shiosaki

Inhibition of p75 tumor necrosis factor receptor by antisense oligonucleotides increases hypoxic injury and beta-amyloid toxicity in human neuronal cell line. J Biol Chem 1997; 272: 3550–3553.

Clinical relevance of plasma ADAM-17 with cognition and neurodegeneration in Alzheimer's disease

Abstract

Background

Objective

Methods

Results

Conclusions

Keywords

Introduction

Methods

Study population

Clinical assessments and diagnosis of AD

Measurements of plasma ADAM-17, Aβ40, Aβ42, t-Tau, and p-Tau181

Statistical analysis

Results

Characteristics of participants

Plasma ADAM-17 is upregulated in AD patients

Plasma ADAM-17 is associated with the AD biomarkers

Plasma ADAM-17 is associated with cognitive functions

Discussion

Footnotes

Acknowledgments

ORCID iDs

Author contributions

Declaration of conflicting interests

Funding

Data availability

References

Measurements of plasma ADAM-17, Aβ₄₀, Aβ₄₂, t-Tau, and p-Tau181