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- W3164750160 abstract "Amyloid formation is that the pathological hallmark of type 2 diabetes (T2D) and Alzheimer’s disease (AD). These diseases are marked by extracellular amyloid deposits of islet amyloid polypeptide (IAPP) within the pancreas and amyloid β (Aβ) within the brain. Since it's been shown that IAPP enters the brain which disparate amyloids can cross-seed one another to reinforce amyloid formation, we determined if such crossseeding can occur with the amyloids involved in T2D and AD. We demonstrated that: (1) IAPP promoted oligomerization of Aβ in vitro and in silico, (2) peripheral injection of IAPP increased murine brain IAPP levels, (3) endogenous IAPP localized to Aβ in plaques in mouse models of AD, (4) IAPP was present in and secreted from astrocytes, and (5) IAPP levels were elevated in AD humor (CSF). These observations prompted us to explore a possible mechanism whereby IAPP elevated during metabolic dysfunction enters the brain to cross-seed Aβ and augment AD pathology. We tested this mechanism in both humans and transgenic mice, correlating peripheral levels of IAPP with AD pathology. In African Americans, a gaggle with increased risk for both T2D and AD, peripheral IAPP levels weren't significantly different in samples with no disease, T2D, AD, or both T2D and AD. Furthermore, within the Tg 2576 AD mouse model, IAPP plasma levels weren't significantly elevated at an age where the mice exhibit the glucose intolerance of pre-diabetes. supported this data, it appears unlikely that peripheral IAPP cross-seeds Aβ pathology in the AD brain. However, we offer evidence for a unique association between brain-derived IAPP and AD, which suggests that brain-derived IAPP plays a task in Aβ oligomerization and AD pathology. This potential connection, together with IAPP’s known role in weight and state of mind, requires further research." @default.
- W3164750160 created "2021-06-07" @default.
- W3164750160 creator A5027818184 @default.
- W3164750160 date "2019-01-01" @default.
- W3164750160 modified "2023-09-27" @default.
- W3164750160 title "PsychoAAD-2013: Islet amyloid polypeptide (IAPP) association with Alzheimerâ??s disease pathology and diagnosis" @default.
- W3164750160 hasPublicationYear "2019" @default.
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