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
Translational Gerontology Branch National Institute on Aging NIH Baltimore Maryland.
Laboratory of Behavioral Neuroscience National Institute on Aging NIH Baltimore Maryland.
Alzheimers Dement (N Y). 2020 May 9;6(1):e12018. doi: 10.1002/trc2.12018. eCollection 2020.
Biomarker discovery of dementia and cognitive impairment is important to gather insight into mechanisms underlying the pathogenesis of these conditions.
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.
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.
These proteins may be useful as non-invasive biomarkers of dementia and cognitive impairment.
痴呆和认知障碍的生物标志物发现对于深入了解这些病症发病机制很重要。
在来自InCHIANTI研究的997名成年人中，我们评估了1301种血浆蛋白与痴呆和认知障碍的关联。在两项阿尔茨海默病（AD）病例对照研究以及AD的内表型（包括认知衰退、脑淀粉样蛋白负荷和脑容量）中进行了验证。
我们鉴定出四种风险蛋白（肽酶抑制剂3（PI3）、三叶因子3（TFF3）、妊娠相关血浆蛋白A（PAPPA）、刺鼠相关肽（AGRP）），其与基线认知障碍或痴呆几率增加显著相关，以及两种保护蛋白（肌肉生长抑制素（MSTN）、整合素αVβ5（ITGAV/ITGB5）），其与基线认知障碍或痴呆几率降低相关。其中，四种蛋白（MSTN、PI3、TFF3、PAPPA）与基线时认知正常的受试者的认知衰退相关。ITGAV/ITGB5与较低的脑淀粉样蛋白负荷相关，MSTN和ITGAV/ITGB5与较大的脑容量和较慢的脑萎缩相关，PI3、PAPPA和AGRP与较小的脑容量和/或较快的脑萎缩相关。
这些蛋白可能作为痴呆和认知障碍的非侵入性生物标志物有用。
