Ly, H;
Verma, N;
Sharma, S;
Kotiya, D;
Despa, S;
Abner, EL;
Nelson, PT;
... Despa, F; + view all
(2021)
The association of circulating amylin with β‐amyloid in familial Alzheimer's disease.
Alzheimer's & Dementia
, 7
(1)
, Article e12130. 10.1002/trc2.12130.
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Abstract
Introduction: This study assessed the hypothesis that circulating human amylin (amyloid‐forming) cross‐seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD). / Methods: Evidence of amylin‐AD pathology interaction was tested in brains of 31 familial AD mutation carriers and 20 cognitively unaffected individuals, in cerebrospinal fluid (CSF) (98 diseased and 117 control samples) and in genetic databases. For functional testing, we genetically manipulated amylin secretion in APP/PS1 and non‐APP/PS1 rats. / Results: Amylin‐Aβ cross‐seeding was identified in AD brains. High CSF amylin levels were associated with decreased CSF Aβ42 concentrations. AD risk and amylin gene are not correlated. Suppressed amylin secretion protected APP/PS1 rats against AD‐associated effects. In contrast, hypersecretion or intravenous injection of human amylin in APP/PS1 rats exacerbated AD‐like pathology through disruption of CSF‐brain Aβ exchange and amylin‐Aβ cross‐seeding. / Discussion: These findings strengthened the hypothesis of circulating amylin‐AD interaction and suggest that modulation of blood amylin levels may alter Aβ‐related pathology/symptoms.
| Type: | Article |
|---|---|
| Title: | The association of circulating amylin with β‐amyloid in familial Alzheimer's disease |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/trc2.12130 |
| Publisher version: | https://doi.org/10.1002/trc2.12130 |
| Language: | English |
| Additional information: | Copyright © 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
| Keywords: | amylin, amyloid, familial Alzheimer's disease, islet amyloid polypeptide, sporadic Alzheimer's disease |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10121630 |
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