TY  - JOUR
UR  - https://doi.org/10.1002/trc2.12130
N1  - 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.
N2  - Introduction: This study assessed the hypothesis that circulating human amylin (amyloid?forming) cross?seeds with amyloid beta (A?) 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?A? cross?seeding was identified in AD brains. High CSF amylin levels were associated with decreased CSF A?42 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 A? exchange and amylin?A? cross?seeding. /

Discussion: These findings strengthened the hypothesis of circulating amylin?AD interaction and suggest that modulation of blood amylin levels may alter A??related pathology/symptoms.
VL  - 7
AV  - public
JF  - Alzheimer's & Dementia
Y1  - 2021///
KW  - amylin
KW  -  amyloid
KW  -  familial Alzheimer's disease
KW  -  islet amyloid polypeptide
KW  -  sporadic Alzheimer's disease
ID  - discovery10121630
IS  - 1
A1  - Ly, H
A1  - Verma, N
A1  - Sharma, S
A1  - Kotiya, D
A1  - Despa, S
A1  - Abner, EL
A1  - Nelson, PT
A1  - Jicha, GA
A1  - Wilcock, DM
A1  - Goldstein, LB
A1  - Guerreiro, R
A1  - Brás, J
A1  - Hanson, AJ
A1  - Craft, S
A1  - Murray, AJ
A1  - Biessels, GJ
A1  - Troakes, C
A1  - Zetterberg, H
A1  - Hardy, J
A1  - Lashley, T
A1  - AESG
A1  - Despa, F
TI  - The association of circulating amylin with ??amyloid in familial Alzheimer's disease
ER  -