Plasma IAPP-Autoantibody Levels in Alzheimer’s Disease Patients Are Affected by <i>APOE4</i> Status
Pancreas-derived islet amyloid polypeptide (IAPP) crosses the blood–brain barrier and co-deposits with amyloid beta (Aβ) in brains of type 2 diabetes (T2D) and Alzheimer’s disease (AD) patients. Depositions might be related to the circulating IAPP levels, but it warrants further investigation. Autoa...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3776 |
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| author | Dovilė Pocevičiūtė Bodil Roth Nina Schultz Cristina Nuñez-Diaz Shorena Janelidze The Netherlands Brain Bank Anders Olofsson Oskar Hansson Malin Wennström |
| author_facet | Dovilė Pocevičiūtė Bodil Roth Nina Schultz Cristina Nuñez-Diaz Shorena Janelidze The Netherlands Brain Bank Anders Olofsson Oskar Hansson Malin Wennström |
| author_sort | Dovilė Pocevičiūtė |
| collection | DOAJ |
| description | Pancreas-derived islet amyloid polypeptide (IAPP) crosses the blood–brain barrier and co-deposits with amyloid beta (Aβ) in brains of type 2 diabetes (T2D) and Alzheimer’s disease (AD) patients. Depositions might be related to the circulating IAPP levels, but it warrants further investigation. Autoantibodies recognizing toxic IAPP oligomers (IAPP<sub>O</sub>) but not monomers (IAPP<sub>M</sub>) or fibrils have been found in T2D, but studies on AD are lacking. In this study, we have analyzed plasma from two cohorts and found that levels of neither immunoglobulin (Ig) M, nor IgG or IgA against IAPP<sub>M</sub> or IAPP<sub>O</sub> were altered in AD patients compared with controls. However, our results show significantly lower IAPP<sub>O</sub>-IgA levels in apolipoprotein E (<i>APOE) 4</i> carriers compared with non-carriers in an allele dose-dependent manner, and the decrease is linked to the AD pathology. Furthermore, plasma IAPP-Ig levels, especially IAPP-IgA, correlated with cognitive decline, C-reactive protein, cerebrospinal fluid Aβ and tau, neurofibrillary tangles, and brain IAPP exclusively in <i>APOE4</i> non-carriers. We speculate that the reduction in IAPP<sub>O</sub>-IgA levels may be caused by increased plasma IAPP<sub>O</sub> levels or masked epitopes in <i>APOE4</i> carriers and propose that IgA and <i>APOE4</i> status play a specific role in clearance of circulatory IAPP<sub>O</sub>, which may influence the amount of IAPP deposition in the AD brain. |
| first_indexed | 2024-03-11T08:42:32Z |
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| id | doaj.art-fce10df1f4304b1096d97963a8c2006a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:42:32Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fce10df1f4304b1096d97963a8c2006a2023-11-16T21:04:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244377610.3390/ijms24043776Plasma IAPP-Autoantibody Levels in Alzheimer’s Disease Patients Are Affected by <i>APOE4</i> StatusDovilė Pocevičiūtė0Bodil Roth1Nina Schultz2Cristina Nuñez-Diaz3Shorena Janelidze4The Netherlands Brain Bank 5Anders Olofsson6Oskar Hansson7Malin Wennström8Cognitive Disorder Research Unit, Department of Clinical Sciences Malmö, Lund University, 214 28 Malmö, SwedenDepartment of Internal Medicine, Lund University, Skåne University Hospital, 214 28 Malmö, SwedenClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, 223 62 Lund, SwedenCognitive Disorder Research Unit, Department of Clinical Sciences Malmö, Lund University, 214 28 Malmö, SwedenClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, 223 62 Lund, SwedenNetherlands Institute for Neuroscience, 1105 BA Amsterdam, The NetherlandsDepartment of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, SwedenClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, 223 62 Lund, SwedenCognitive Disorder Research Unit, Department of Clinical Sciences Malmö, Lund University, 214 28 Malmö, SwedenPancreas-derived islet amyloid polypeptide (IAPP) crosses the blood–brain barrier and co-deposits with amyloid beta (Aβ) in brains of type 2 diabetes (T2D) and Alzheimer’s disease (AD) patients. Depositions might be related to the circulating IAPP levels, but it warrants further investigation. Autoantibodies recognizing toxic IAPP oligomers (IAPP<sub>O</sub>) but not monomers (IAPP<sub>M</sub>) or fibrils have been found in T2D, but studies on AD are lacking. In this study, we have analyzed plasma from two cohorts and found that levels of neither immunoglobulin (Ig) M, nor IgG or IgA against IAPP<sub>M</sub> or IAPP<sub>O</sub> were altered in AD patients compared with controls. However, our results show significantly lower IAPP<sub>O</sub>-IgA levels in apolipoprotein E (<i>APOE) 4</i> carriers compared with non-carriers in an allele dose-dependent manner, and the decrease is linked to the AD pathology. Furthermore, plasma IAPP-Ig levels, especially IAPP-IgA, correlated with cognitive decline, C-reactive protein, cerebrospinal fluid Aβ and tau, neurofibrillary tangles, and brain IAPP exclusively in <i>APOE4</i> non-carriers. We speculate that the reduction in IAPP<sub>O</sub>-IgA levels may be caused by increased plasma IAPP<sub>O</sub> levels or masked epitopes in <i>APOE4</i> carriers and propose that IgA and <i>APOE4</i> status play a specific role in clearance of circulatory IAPP<sub>O</sub>, which may influence the amount of IAPP deposition in the AD brain.https://www.mdpi.com/1422-0067/24/4/3776ADamylinamyloid beta<i>APOE4</i>autoantibodiescognition |
| spellingShingle | Dovilė Pocevičiūtė Bodil Roth Nina Schultz Cristina Nuñez-Diaz Shorena Janelidze The Netherlands Brain Bank Anders Olofsson Oskar Hansson Malin Wennström Plasma IAPP-Autoantibody Levels in Alzheimer’s Disease Patients Are Affected by <i>APOE4</i> Status International Journal of Molecular Sciences AD amylin amyloid beta <i>APOE4</i> autoantibodies cognition |
| title | Plasma IAPP-Autoantibody Levels in Alzheimer’s Disease Patients Are Affected by <i>APOE4</i> Status |
| title_full | Plasma IAPP-Autoantibody Levels in Alzheimer’s Disease Patients Are Affected by <i>APOE4</i> Status |
| title_fullStr | Plasma IAPP-Autoantibody Levels in Alzheimer’s Disease Patients Are Affected by <i>APOE4</i> Status |
| title_full_unstemmed | Plasma IAPP-Autoantibody Levels in Alzheimer’s Disease Patients Are Affected by <i>APOE4</i> Status |
| title_short | Plasma IAPP-Autoantibody Levels in Alzheimer’s Disease Patients Are Affected by <i>APOE4</i> Status |
| title_sort | plasma iapp autoantibody levels in alzheimer s disease patients are affected by i apoe4 i status |
| topic | AD amylin amyloid beta <i>APOE4</i> autoantibodies cognition |
| url | https://www.mdpi.com/1422-0067/24/4/3776 |
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