Islet amyloid polypeptide & amyloid beta peptide roles in Alzheimer's disease: Two triggers, one disease

Sofia Ferreira, Ana Raimundo, Regina Menezes, Ivo Martins

Research output: Contribution to journalReview articlepeer-review

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Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that affects millions worldwide. Due to population ageing, the incidence of AD is increasing. AD patients develop cognitive decline and dementia, features for which is known, requiring permanent care. This poses a major socio-economic burden on healthcare systems as AD patients' relatives and healthcare workers are forced to cope with rising numbers of affected people. Despite recent advances, AD pathological mechanisms are not fully understood. Nevertheless, it is clear that the amyloid beta (Aβ) peptide, which forms amyloid plaques in AD patients' brains, plays a key role. Type 2 diabetes, the most common form of diabetes, affects hundreds of million people globally. Islet amyloid polypeptide (IAPP) is a hormone co-produced and secreted with insulin in pancreatic β-cells, with a key role in diabetes, as it helps regulate glucose levels and control adiposity and satiation. Similarly to Aβ, IAPP is very amyloidogenic, generating intracellular amyloid deposits that cause β-cell dysfunction and death. It is now clear that IAPP can also have a pathological role in AD, decreasing cognitive function. IAPP harms the blood-brain barrier, directly interacts and co-deposits with Aβ, promoting diabetes-associated dementia. IAPP can cause a metabolic dysfunction in the brain, leading to other diabetes-related forms of AD. Thus, here we discuss IAPP association with diabetes, Aβ and dementia, in the context of what we designate a 'diabetes brain phenotype' AD hypothesis. Such approach helps to set a conceptual framework for future IAPP-based drugs against AD.

Original languageEnglish
Pages (from-to)1127-1130
Number of pages4
JournalNeural Regeneration Research
Volume16
Issue number6
DOIs
Publication statusPublished - Jun 2021

Keywords

  • aggregation
  • Alzheimer
  • amylin
  • amyloid
  • diabetes
  • islet amyloid polypeptide

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