Dataset Information

The association of circulating amylin with ?-amyloid in familial Alzheimer's disease.

ABSTRACT:

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.

SUBMITTER: Ly H

PROVIDER: S-EPMC7816817 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

The association of circulating amylin with β-amyloid in familial Alzheimer's disease.

Ly Han H Verma Nirmal N Sharma Savita S Kotiya Deepak D Despa Sanda S Abner Erin L EL Nelson Peter T PT Jicha Gregory A GA Wilcock Donna M DM Goldstein Larry B LB Guerreiro Rita R Brás José J Hanson Angela J AJ Craft Suzanne S Murray Andrew J AJ Biessels Geert Jan GJ Troakes Claire C Zetterberg Henrik H Hardy John J Lashley Tammaryn T Aesg Despa Florin F

Alzheimer's & dementia (New York, N. Y.) 20210120 1

<h4>Introduction</h4>This study assessed the hypothesis that circulating human amylin (amyloid-forming) cross-seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD).<h4>Methods</h4>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 ...[more]

PMID: 33521236