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Inflammatory biomarkers in Alzheimer's disease plasma.

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Peer-reviewed

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Article

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Authors

Morgan, Angharad R 
Touchard, Samuel 
Leckey, Claire 
O'Hagan, Caroline 
Nevado-Holgado, Alejo J 

Abstract

INTRODUCTION: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a "Holy Grail" of AD research and intensively sought; however, there are no well-established plasma markers. METHODS: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. RESULTS: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). DISCUSSION: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation.

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Keywords

Alzheimer's disease, Biomarker, Complement, Inflammation, Plasma, Aged, Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, Cognitive Dysfunction, Cohort Studies, Complement Factor B, Complement Factor H, Humans, Inflammation, Internationality, Prognosis

Journal Title

Alzheimers Dement

Conference Name

Journal ISSN

1552-5260
1552-5279

Volume Title

15

Publisher

Wiley
Sponsorship
Wellcome Trust (104025/Z/14/Z)
MQ: Transforming Mental Health (MQ17-24 Vertes)
Wellcome Trust (203249/Z/16/Z)