Open AccessPlasma proteomic signatures predict dementia and cognitive impairment
Author(s) -
Tanaka Toshiko,
Lavery Robert,
Varma Vijay,
Fantoni Giovanna,
Colpo Marco,
Thambisetty Madhav,
Candia Julian,
Resnick Susan M.,
Bennett David A.,
Biancotto Angelique,
Bandinelli Stefania,
Ferrucci Luigi
Publication year - 2020
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/trc2.12018
Subject(s) - dementia , biomarker , medicine , atrophy , alzheimer's disease , oncology , cognitive impairment , cognitive decline , brain size , disease , neuroscience , bioinformatics , psychology , magnetic resonance imaging , biology , genetics , radiology
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.