Proteomics analysis of plasma from middle-aged adults identifies protein markers of dementia risk in later life

I can't imagine any hospital using this to test for dementia risk; so useless.  And with NO protocols to prevent dementia, doubly useless.

What is the method of proteomics analysis?

The techniques that are most often used are electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI). Both of them are representatives of so-called soft ionization techniques in which ions are created with low internal energies and thus undergo little fragmentation.

Proteomics analysis of plasma from middle-aged adults identifies protein markers of dementia risk in later life

Keenan A. Walker https://orcid.org/0000-0002-5989-9853 , Jingsha Chen, Liu Shi, Yunju Yang https://orcid.org/0000-0002-9747-8363, Myriam Fornage https://orcid.org/0000-0003-0677-8158, Linda Zhou, Pascal Schlosser https://orcid.org/0000-0002-8460-0462, Aditya Surapaneni https://orcid.org/0000-0003-4978-5980, Morgan E. Grams https://orcid.org/0000-0002-4430-6023, [...] , and Josef Coresh https://orcid.org/0000-0002-4598-0669 +15 authors Authors Info & Affiliations

Science Translational Medicine

19 Jul 2023

Vol 15, Issue 705

DOI: 10.1126/scitranslmed.adf5681

Abstract

A diverse set of biological processes have been implicated in the pathophysiology of Alzheimer’s disease (AD) and related dementias. However, there is limited understanding of the peripheral biological mechanisms relevant in the earliest phases of the disease. Here, we used a large-scale proteomics platform to examine the association of 4877 plasma proteins with 25-year dementia risk in 10,981 middle-aged adults. We found 32 dementia-associated plasma proteins that were involved in proteostasis, immunity, synaptic function, and extracellular matrix organization. We then replicated the association between 15 of these proteins and clinically relevant neurocognitive outcomes in two independent cohorts. We demonstrated that 12 of these 32 dementia-associated proteins were associated with cerebrospinal fluid (CSF) biomarkers of AD, neurodegeneration, or neuroinflammation. We found that eight of these candidate protein markers were abnormally expressed in human postmortem brain tissue from patients with AD, although some of the proteins that were most strongly associated with dementia risk, such as GDF15, were not detected in these brain tissue samples. Using network analyses, we found a protein signature for dementia risk that was characterized by dysregulation of specific immune and proteostasis/autophagy pathways in adults in midlife ~20 years before dementia onset, as well as abnormal coagulation and complement signaling ~10 years before dementia onset. Bidirectional two-sample Mendelian randomization genetically validated nine of our candidate proteins as markers of AD in midlife and inferred causality of SERPINA3 in AD pathogenesis. Last, we prioritized a set of candidate markers for AD and dementia risk prediction in midlife.

Editor’s summary

Pathological changes involved in Alzheimer’s disease (AD) occur decades before the onset of cognitive deficits but are not well understood. Here, Walker and colleagues used proteomics and genomics on a cohort of middle-aged adults followed longitudinally and identified pathway-specific plasma proteins that increased dementia risk up to 25 years later. The pathway signature of these proteins was characterized by dysregulated immune signaling and proteostasis in the earliest preclinical stages and abnormal coagulation and complement signaling around 10 years before dementia onset. The study indicates that distinct biological mechanisms may be relevant in earlier and later preclinical stages of AD. –Daniela Neuhofer

Get full access to this article