Plasma IAPP-Autoantibody Levels in Alzheimer’s Disease Patients Are Affected by APOE4 Status
(2023) In International Journal of Molecular Sciences 24(4).- Abstract
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 (IAPPO) but not monomers (IAPPM) 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 IAPPM or IAPPO were altered in AD patients compared with controls. However, our results show significantly lower... (More)
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 (IAPPO) but not monomers (IAPPM) 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 IAPPM or IAPPO were altered in AD patients compared with controls. However, our results show significantly lower IAPPO-IgA levels in apolipoprotein E (APOE) 4 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 APOE4 non-carriers. We speculate that the reduction in IAPPO-IgA levels may be caused by increased plasma IAPPO levels or masked epitopes in APOE4 carriers and propose that IgA and APOE4 status play a specific role in clearance of circulatory IAPPO, which may influence the amount of IAPP deposition in the AD brain.
(Less)
- author
- Pocevičiūtė, Dovilė LU ; Roth, Bodil LU ; Schultz, Nina LU ; Nuñez-Diaz, Cristina LU ; Janelidze, Shorena LU ; Olofsson, Anders ; Hansson, Oskar LU and Wennström, Malin LU
- author collaboration
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- AD, amylin, amyloid beta, APOE4, autoantibodies, cognition, IgA, IgG, IgM, T2D
- in
- International Journal of Molecular Sciences
- volume
- 24
- issue
- 4
- article number
- 3776
- publisher
- MDPI AG
- external identifiers
-
- scopus:85149143255
- pmid:36835187
- ISSN
- 1661-6596
- DOI
- 10.3390/ijms24043776
- language
- English
- LU publication?
- yes
- id
- 187bda85-b466-4753-9388-e1008f2003e0
- date added to LUP
- 2023-03-20 11:26:37
- date last changed
- 2024-04-18 19:27:51
@article{187bda85-b466-4753-9388-e1008f2003e0, abstract = {{<p>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 (APOE) 4 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 APOE4 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 APOE4 carriers and propose that IgA and APOE4 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.</p>}}, author = {{Pocevičiūtė, Dovilė and Roth, Bodil and Schultz, Nina and Nuñez-Diaz, Cristina and Janelidze, Shorena and Olofsson, Anders and Hansson, Oskar and Wennström, Malin}}, issn = {{1661-6596}}, keywords = {{AD; amylin; amyloid beta; APOE4; autoantibodies; cognition; IgA; IgG; IgM; T2D}}, language = {{eng}}, number = {{4}}, publisher = {{MDPI AG}}, series = {{International Journal of Molecular Sciences}}, title = {{Plasma IAPP-Autoantibody Levels in Alzheimer’s Disease Patients Are Affected by APOE4 Status}}, url = {{http://dx.doi.org/10.3390/ijms24043776}}, doi = {{10.3390/ijms24043776}}, volume = {{24}}, year = {{2023}}, }