Is islet amyloid polypeptide indeed expressed in the human brain?

• Published in: Neuropathology and applied neurobiology Vol. 49; no. 4; pp. e12917 - n/a
• Main Authors: Libard, Sylwia, Alafuzoff, Irina
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.08.2023
• Subjects: Alzheimer's disease; Alzheimer's disease neuropathological change; Amylin; beta-amyloid; Biopsy; Brain; Epitopes; Hydrocephalus; idiopathic normal pressure hydrocephalus; islet amyloid polypeptide; Monoclonal antibodies; Neurodegenerative diseases; Pathology; Polypeptides; type 2 diabetes mellitus; β-Amyloid; Alzheimer’s disease; idiopathic normal pressure hydrocephalus; type 2 Diabetes mellitus; Islet amyloid polypeptide, amylin, beta-amyloid, Alzheimer’s disease neuropathological change
• ISSN: 0305-1846; 1365-2990; 1365-2990
• DOI: 10.1111/nan.12917

Aims This study aims to study the association between pancreatic islet amyloid polypeptide (IAPP) and Alzheimer's disease neuropathological change (ADNC) in brain biopsies obtained from subjects with idiopathic normal pressure hydrocephalus (iNPH) and in post‐mortem (PM) brain samples obtained from aged individuals. Methods For the immunohistochemical (IHC) analyses, two IAPP antibodies (Abs), monoclonal and polyclonal, and Abs directed towards ADNC were applied. Results The iNPH cohort included 113 subjects. Amyloid‐β (Aβ) was detected in 50% and hyperphosphorylated τ (HPτ) in 47% of the cases. Concomitant pathology was seen in 32%. The PM cohort included 77 subjects. Aβ was detected in 69% and HPτ in 91% of the cases. Combined Aβ/HPτ pathology was seen in 62%. Reactivity for the monoclonal IAPP was not detected in the brain tissue in either of the cohorts. Reactivity for the polyclonal IAPP was observed in all 77 PM brain samples. Conclusions There was no specific expression of IAPP in human brain tissue; hence, an association between IAPP and ADNC is not assessable. Of note, the observed reactivity of the polyclonal IAPP Ab was not reproduced with a specific monoclonal Ab; thus, we considered the observed staining with the polyclonal Ab to be unreliable. When using IHC, several pitfalls, especially the choice of an Ab, always need to be considered. Polyclonal Abs cross‐react with other epitopes and proteins, thus leading to false‐positive results. This seems to be the case for the polyclonal IAPP Abs in the human brain. We have studied the association between Alzheimer's disease neuropathological change (ADNC) and islet amyloid polypeptide (IAPP) in surgical brain biopsies from idiopathic normal pressure hydrocephalus patients and in post‐mortem brain samples from aged subjects, as in previous studies, IAPP has been detected within human brains. There was no specific IAPP expression in neither of our cohorts, hence no association between ADNC and IAPP. Noteworthy, a non‐specific IAPP expression was observed, applying a polyclonal IAPP antibody, due to a methodological pitfall.