Open AccessThe association of circulating amylin with β‐amyloid in familial Alzheimer's disease
Author(s) -
Ly Han,
Verma Nirmal,
Sharma Savita,
Kotiya Deepak,
Despa Sanda,
Abner Erin L.,
Nelson Peter T.,
Jicha Gregory A.,
Wilcock Donna M.,
Goldstein Larry B.,
Guerreiro Rita,
Brás José,
Hanson Angela J.,
Craft Suzanne,
Murray Andrew J.,
Biessels Geert Jan,
Troakes Claire,
Zetterberg Henrik,
Hardy John,
Lashley Tammaryn,
Despa Florin
Publication year - 2021
Publication title -
alzheimer's and dementia: translational research and clinical interventions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.49
H-Index - 30
ISSN - 2352-8737
DOI - 10.1002/trc2.12130
Subject(s) - amylin , amyloid (mycology) , medicine , endocrinology , cerebrospinal fluid , alzheimer's disease , disease , pathology , diabetes mellitus , islet
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 Aβ 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 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.