Islet Amyloid Polypeptide (IAPP): A Second Amyloid in Alzheimer&amp;#39;s Disease

Fawver, Janelle N.; Ghiwot, Yonatan; Koola, Catherine; Carrera, Wesley; Rodriguez-Rivera, Jennifer; Hernandez, Caterina M.; Dineley, Kelly T.; Kong, Yu; Lǐ, Jiànróng; Jhamandas, Jack H.; Perry, George; Murray, Ian V.J.

doi:10.2174/1567205011666141107124538

Cited by 86 publications

(97 citation statements)

References 84 publications

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“…This idea is supported by in vitro studies showing that IAPP and Aβ can cross-seed each other, stimulating amyloid formation [152,153]. In addition, IAPP has been found associated to amyloid plaques in AD patients [153]. Further, Aβ deposits and hyperphosphorylated tau, hallmark features of AD, have been reported in the islets of T2D patients [154], and the majority of Aβ colocalized with IAPP aggregates in severely affected areas.…”

Section: Iapp Aggregates In Non-pancreatic Tissuesmentioning

confidence: 93%

“…Another interesting possibility is that misfolded proteins implicated in AD and T2D may interact between each other, promoting their heterologous seeding and accelerating the pathological onset [149]. This idea is supported by in vitro studies showing that IAPP and Aβ can cross-seed each other, stimulating amyloid formation [152,153]. In addition, IAPP has been found associated to amyloid plaques in AD patients [153].…”

Section: Iapp Aggregates In Non-pancreatic Tissuesmentioning

confidence: 99%

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Type 2 diabetes as a protein misfolding disease

Mukherjee¹,

Morales-Scheihing²,

Butler³

et al. 2015

Trends in Molecular Medicine

279

202

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Type 2 diabetes is a highly prevalent and chronic metabolic disorder. Recent evidence suggests that formation of toxic aggregates of the islet amyloid polypeptide (IAPP) might contribute to β-cell dysfunction and disease. However, the mechanism of protein aggregation and associated toxicity is still unclear. Misfolding, aggregation and accumulation of diverse proteins in different organs is the hallmark in the group of protein misfolding disorders (PMDs), including highly prevalent illnesses affecting the central nervous system such as Alzheimer’s and Parkinson’s diseases. In this review we will discuss the current understanding of the mechanisms implicated in the formation of protein aggregates in pancreas and associated toxicity in the light of the longstanding knowledge from neurodegenerative disorders associated with protein misfolding.

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Section: Iapp Aggregates In Non-pancreatic Tissuesmentioning

confidence: 93%

Section: Iapp Aggregates In Non-pancreatic Tissuesmentioning

confidence: 99%

Type 2 diabetes as a protein misfolding disease

Mukherjee¹,

Morales-Scheihing²,

Butler³

et al. 2015

Trends in Molecular Medicine

279

202

View full text Add to dashboard Cite

show abstract

“…These results [10] were interpreted as a possible effect of IR, which is common in aging. Notably, two other laboratories [11,12] independently demonstrated amylin deposition [11,12] and amylin-Aβ plaque formation [12] in brains of dementia patients. However, the potential link between brain amylin deposition and increased risk of cognitive decline has not been systematically evaluated.…”

mentioning

confidence: 99%

Hyperamylinemia as a risk factor for accelerated cognitive decline in diabetes

Despa²

2015

Expert Review of Proteomics

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Type II diabetes increases the risk for cognitive decline via multiple traits. Amylin is a pancreatic hormone that has amyloidogenic and cytotoxic properties similar to the amyloid-β peptide. The amylin hormone is overexpressed in individuals with pre-diabetic insulin resistance or obesity leading to amylin oligomerization and deposition in pancreatic islets. Amylin oligomerization was implicated in the apoptosis of the insulin-producing β-cells. Recent studies showed that brain tissue from diabetic patients with cerebrovascular dementia or Alzheimer’s disease contains significant deposits of oligomerized amylin. It has also been reported that the brain amylin deposition reduced exploratory drive, recognition memory and vestibulomotor function in a rat model that overexpresses human amylin in the pancreas. These novel findings are reviewed here and the hypothesis that type II diabetes is linked with cognitive decline by amylin accumulation in the brain is proposed. Deciphering the impact of hyperamylinemia on the brain is critical for both etiology and treatment of dementia.

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“…Some data suggest that amylin may play a vital role at the interface between peripheral and neurodegenerative disorders, and that amylin and Aβ interact in the brain [51]. Evidence to support the latter includes PIAPP being present in human cerebrospinal fluid (CSF), synthetic PIAPP promoting Aβ oligomerization in vitro and endogenous IAPP localizing to Aβ oligomers and plaques [52]. While higher levels of blood amylin are associated with higher BMI, lower blood levels of amylin have been observed in adults with more severe forms of cognitive impairment, such as dementia [18].…”

Section: Discussionmentioning

confidence: 99%

Ghrelin, Amylin, Gastric Inhibitory Peptide and Cognition in Middle-Aged HIV-Infected and Uninfected Women: The Women’s Interagency HIV Study

McFarlane

Mielke

Uglialoro

et al. 2017

J Neurol Neurophysiol

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Objective To explore the gut-brain axis by examining gut hormone levels and cognitive test scores in women with (HIV+) and without (HIV−) HIV infection. Design/methods Participants included 356 women (248 HIV+, 108 at risk HIV−) in the Brooklyn Women’s Interagency HIV Study (WIHS) with measured levels of ghrelin, amylin and gastric inhibitory peptide (GIP), also known as glucose-dependent insulinotropic polypeptide. Cross-sectional analyses using linear regression models estimated the relationship between gut hormones and Trails A, Trails B, Stroop interference time, Stroop word recall, Stroop color naming and reading, and Symbol Digit Modalities Test (SDMT) with consideration for age, HIV infection status, Wide Range Achievement Test score (WRAT), CD4 count, insulin resistance, drug use, and race/ethnicity. Results Among women at mid-life with chronic (at least 10 years) HIV infection or among those at risk, ghrelin, amylin and GIP were differentially related to cognitive test performance by cognitive domain. Better performance on cognitive tests was generally associated with higher ghrelin, amylin and GIP levels. However, the strength of association varied, as did significance level by HIV status. Conclusion Previous analyses in WIHS participants have suggested that higher BMI, waist, and WHR are associated with better cognitive function among women at mid-life with HIV infection. This study indicates that higher gut hormone levels are also associated with better cognition. Gut hormones may provide additional mechanistic insights regarding the association between obesity and Type 2 diabetes and cognition in middle-aged HIV+ and at risk HIV− women. In addition, measuring these hormones longitudinally would add to the understanding of mechanisms of actions of these hormones and their use as potential clinical tools for early identification and intervention on cognitive decline in this vulnerable population.

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Islet Amyloid Polypeptide (IAPP): A Second Amyloid in Alzheimer's Disease

Cited by 86 publications

References 84 publications

Type 2 diabetes as a protein misfolding disease

Type 2 diabetes as a protein misfolding disease

Hyperamylinemia as a risk factor for accelerated cognitive decline in diabetes

Ghrelin, Amylin, Gastric Inhibitory Peptide and Cognition in Middle-Aged HIV-Infected and Uninfected Women: The Women’s Interagency HIV Study

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