Plasma proteomic signatures predict dementia and cognitive impairment.

Abstract

INTRODUCTION:

Biomarker discovery of dementia and cognitive impairment is important to gather insight into mechanisms underlying the pathogenesis of these conditions.

METHODS:

In 997 adults from the InCHIANTI study, we assessed the association of 1301 plasma proteins with dementia and cognitive impairment. Validation was conducted in two Alzheimer's disease (AD) case-control studies as well as endophenotypes of AD including cognitive decline, brain amyloid burden, and brain volume.

RESULTS:

We identified four risk proteins that were significantly associated with increased odds (peptidase inhibitor 3 (PI3), trefoil factor 3 (TFF3), pregnancy associated plasma protein A (PAPPA), agouti-related peptide (AGRP)) and two protective proteins (myostatin (MSTN), integrin aVb5 (ITGAV/ITGB5)) with decreased odds of baseline cognitive impairment or dementia. Of these, four proteins (MSTN, PI3, TFF3, PAPPA) were associated cognitive decline in subjects that were cognitively normal at baseline. ITGAV/ITGB5 was associated with lower brain amyloid burden, MSTN and ITGAV/ITGB5 were associated with larger brain volume and slower brain atrophy, and PI3, PAPPA, and AGRP were associated with smaller brain volume and/or faster brain atrophy.

DISCUSSION:

These proteins may be useful as non-invasive biomarkers of dementia and cognitive impairment.

• Authors: Toshiko Tanaka, Robert Lavery, Vijay Varma, Giovanna Fantoni, Marco Colpo, Madhav Thambisetty, Julian Candia, Susan M Resnick, David A Bennett, Angelique Biancotto, Stefania Bandinelli, Luigi Ferrucci
• Journal: Alzheimer's & dementia (New York, N. Y.) (Alzheimers Dement (N Y)) Vol. 6 Issue 1 Pg. e12018 ( 2020) ISSN: 2352-8737 [Electronic] United States
• PMID: 32607407 (Publication Type: Journal Article)
• Copyright: Published 2020. This article is a U.S. Government work and is in the public domain in the USA. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc on behalf of Alzheimer's Association.