Exploratory Assessment of Proteomic Network Changes in Cerebrospinal Fluid of Mild Cognitive Impairment Patients: A Pilot Study

Kamalian, Aida; Ho, Stanley; Patel, Mehul S.; Lewis, Alexandria; Bakker, Arnold B.; Albert, Marilyn; O’Brien, Richard; Moghekar, Abhay; Lutz, Michael W.

doi:10.3390/biom13071094

Cited by 6 publications

(1 citation statement)

References 44 publications

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“…Several proteins that have been identified as upregulated in WML and mediating WMLassociated cognitive decline also exhibit heightened levels in an AD context 75,76 . Among these, cystatin B (CSTB) and NEFL stand out for their notable mediation effects.…”

Section: Discussionmentioning

confidence: 99%

Identification of distinct and shared biomarker panels in different manifestations of cerebral small vessel disease through proteomic profiling

Hristovska,

Binette,

Kumar

et al. 2024

Preprint

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The pathophysiology underlying various manifestations of cerebral small vessel disease (cSVD) remains obscure. Using cerebrospinal fluid proximity extension assays and co-expression network analysis of 2,943 proteins, we found common and distinct proteomic signatures between white matter lesions (WML), microbleeds and infarcts measured in 856 living patients, and validated WML-associated proteins in three additional datasets. Proteins indicative of extracellular matrix dysregulation and vascular remodeling, including ELN, POSTN, CCN2 and MMP12 were elevated across all cSVD manifestations, with MMP12 emerging as an early cSVD indicator. cSVD-associated proteins formed a co-abundance network linked to metabolism and enriched in endothelial and arterial smooth muscle cells, showing elevated levels at early disease manifestations. Later disease stages involved changes in microglial proteins, associated with longitudinal WML progression, and changes in neuronal proteins mediating WML-associated cognitive decline. These findings provide an atlas of novel cSVD biomarkers and a promising roadmap for the next generation of cSVD therapeutics.

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Section: Discussionmentioning

confidence: 99%

Identification of distinct and shared biomarker panels in different manifestations of cerebral small vessel disease through proteomic profiling

Hristovska,

Binette,

Kumar

et al. 2024

Preprint

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Methods and clinical biomarker discovery for targeted proteomics using Olink technology

Wang,

Zhao,

Zeng

et al. 2024

Proteomics Clinical Apps

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PurposeThis paper is to offer insights for designing research utilizing Olink technology to identify biomarkers and potential therapeutic targets for disease treatment.Experimental DesignWe discusses the application of Olink technology in oncology, cardiovascular, respiratory and immune‐related diseases, and Outlines the advantages and limitations of Olink technology.ResultsOlink technology simplifies the search for therapeutic targets, advances proteomics research, reveals the pathogenesis of diseases, and ultimately helps patients develop precision treatments.ConclusionsAlthough proteomics technology has been rapidly developed in recent years, each method has its own disadvantages, so in the future research, more methods should be selected for combined application to verify each other.

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SMOC1 colocalizes with Alzheimer’s disease neuropathology and delays Aβ aggregation

Balcomb,

Johnston,

Kavanagh

et al. 2024

Acta Neuropathol

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SMOC1 has emerged as one of the most significant and consistent new biomarkers of early Alzheimer’s disease (AD). Recent studies show that SMOC1 is one of the earliest changing proteins in AD, with levels in the cerebrospinal fluid increasing many years before symptom onset. Despite this clear association with disease, little is known about the role of SMOC1 in AD or its function in the brain. Therefore, the aim of this study was to examine the distribution of SMOC1 in human AD brain tissue and to determine if SMOC1 influenced amyloid beta (Aβ) aggregation. The distribution of SMOC1 in human brain tissue was assessed in 3 brain regions (temporal cortex, hippocampus, and frontal cortex) using immunohistochemistry in a cohort of 73 cases encompassing advanced AD, mild cognitive impairment (MCI), preclinical AD, and cognitively normal controls. The Aβ- and phosphorylated tau-interaction with SMOC1 was assessed in control, MCI, and advanced AD human brain tissue using co-immunoprecipitation, and the influence of SMOC1 on Aβ aggregation kinetics was assessed using Thioflavin-T assays and electron microscopy. SMOC1 strongly colocalized with a subpopulation of amyloid plaques in AD (43.8 ± 2.4%), MCI (32.8 ± 5.4%), and preclinical AD (28.3 ± 6.4%). SMOC1 levels in the brain strongly correlated with plaque load, irrespective of disease stage. SMOC1 also colocalized with a subpopulation of phosphorylated tau aggregates in AD (9.6 ± 2.6%). Co-immunoprecipitation studies showed that SMOC1 strongly interacted with Aβ in human MCI and AD brain tissue and with phosphorylated tau in human AD brain tissue. Thioflavin-T aggregation assays showed that SMOC1 significantly delayed Aβ aggregation in a dose-dependent manner, and electron microscopy confirmed that the Aβ fibrils generated in the presence of SMOC1 had an altered morphology. Overall, our results emphasize the importance of SMOC1 in the onset and progression of AD and suggest that SMOC1 may influence pathology development in AD.

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Exploratory Assessment of Proteomic Network Changes in Cerebrospinal Fluid of Mild Cognitive Impairment Patients: A Pilot Study

Cited by 6 publications

References 44 publications

Identification of distinct and shared biomarker panels in different manifestations of cerebral small vessel disease through proteomic profiling

Identification of distinct and shared biomarker panels in different manifestations of cerebral small vessel disease through proteomic profiling

Methods and clinical biomarker discovery for targeted proteomics using Olink technology

SMOC1 colocalizes with Alzheimer’s disease neuropathology and delays Aβ aggregation

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