Novel Hominid-Specific IAPP Isoforms: Potential Biomarkers of Early Alzheimer's Disease and Inhibitors of Amyloid Formation.
Hominid-specific IAPP isoforms may serve as potential biomarkers for early Alzheimer's disease, but further validation is necessary to confirm their clinical utility.
Where it sits
this study against the rest of the dnsp-11 (dopamine neuron stimulating peptide-11) corpusSummary and findings
This study aimed to identify potential biomarkers for early Alzheimer's disease (AD) and assess the anti-amyloid properties of novel IAPP isoforms and DNSP-11. The research involved measuring peptide levels in human plasma and cerebrospinal fluid (CSF) from individuals with early AD and controls. The findings suggest that hIAPPβ is significantly reduced in AD patients' plasma, with an accuracy of 89%.
Abstract
(1) Background and aims: Amyloidosis due to aggregation of amyloid-β (Aβ<sub>42</sub>) is a key pathogenic event in Alzheimer's disease (AD), whereas aggregation of mature islet amyloid polypeptide (IAPP<sub>37</sub>) in human islets leads to β-cell dysfunction. The aim of this study is to uncover potential biomarkers that might additionally point to therapy for early AD patients. (2) Methods: We used bioinformatic approach to uncover novel IAPP isoforms and developed a quantitative selective reaction monitoring (SRM) proteomic assay to measure their peptide levels in human plasma and CSF from individuals with early AD and controls, as well as postmortem cerebrum of clinical confirmed AD and controls. We used Thioflavin T amyloid reporter assay to measure the IAPP isoform fibrillation propensity and anti-amyloid potential against aggregation of Aβ<sub>42</sub> and IAPP<sub>37</sub>. (3) Results: We uncovered hominid-specific IAPP isoforms: hIAPPβ, which encodes an elongated propeptide, and hIAPPγ, which is processed to mature IAPP<sub>25</sub> instead of IAPP<sub>37</sub>. We found that hIAPPβ was significantly reduced in the plasma of AD patients with the accuracy of 89%. We uncovered that IAPP<sub>25</sub> and a GDNF derived DNSP<sub>11</sub> were nonaggregating peptides that inhibited the aggregation of IAPP<sub>37</sub> and Aβ<sub>42</sub>. (4) Conclusions: The novel peptides derived from hIAPP isoforms have potential to serve as blood-derived biomarkers for early AD and be developed as peptide based anti-amyloid medicine.
Background
The paper addresses the biological question of whether novel hominid-specific IAPP isoforms can serve as biomarkers for early Alzheimer's disease and their potential role in inhibiting amyloid formation. Prior research has indicated that IAPP may be involved in amyloid pathology, but the specific isoforms and their implications in Alzheimer's disease remain unclear. This study aims to fill that gap by exploring these isoforms in the context of Alzheimer's.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Key findings
- Not reported in abstract.
Limitations
- Not reported in abstract.