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

Introduction This study assessed the hypothesis that circulating human amylin (amyloid-forming) cross-seeds with amyloid beta (A beta) 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 beta cross-seeding was identified in AD brains. High CSF amylin levels were associated with decreased CSF A beta(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 beta exchange and amylin-A beta cross-seeding. Discussion These findings strengthened the hypothesis of circulating amylin-AD interaction and suggest that modulation of blood amylin levels may alter A beta-related pathology/symptoms.

Automated summary

This study found cross-seeding of amylin-Aβ in the brains of AD patients. High levels of amylin in the CSF were associated with decreased Aβ(42) concentrations. The risk of AD and the amylin gene are not correlated.