Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease

Chatterjee, Pratishtha; Pedrini, Steve; Ashton, Nicholas J.; Tegg, Michelle; Goozee, Kathryn; Singh, Abhay Kumar; Karikari, Thomas K.; Simrén, Joel; Vanmechelen, Eugeen; Armstrong, Nicola J.; Hone, Eugene; Asih, Prita R.; Taddei, Kevin; Doré, Vincent; Villemagne, Victor L.; Sohrabi, Hamid R.; Zetterberg, Henrik; Masters, Colin L.; Blennow, Kaj; Martins, Ralph N.

doi:10.1002/alz.12447

Cited by 138 publications

(143 citation statements)

References 44 publications

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“…In recent years, many studies have reported the close relationship between GFAP and AD. Chatterjee et al [ 33 ]. used Simoa assay to measure plasma proteins in cognitively unimpaired older adults (CU) and found that GFAP and p-tau181 were upregulated in the CU group with cerebral amyloidosis, which indicated the clinical potential of GFAP and p-tau for the diagnosis and longitudinal monitoring of preclinical AD.…”

Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes and Immune Cell Infiltration Characteristics in Alzheimer’s Disease

Wang

2021

Journal of Healthcare Engineering

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The purpose of this study was to identify hub genes closely correlated with Alzheimer's disease (AD) and their association with immune cell infiltration. In this work, 119 overlapping differentially expressed genes (DEGs) were obtained from GSE5281 and GSE122063 datasets through differential expression analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the 119 DEGs, revealing some important biological functions and key pathways. AD immune cell infiltration analysis revealed a significant difference in the proportion of immune cells between the AD group and the control group. Finally, correlation analysis between target hub genes and immune cells indicated that GFAP had a positive or negative correlation with some specific immune cells. Our results provided useful clues, which will help to explain the molecular mechanism of AD and search for precise prognostic markers and potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes and Immune Cell Infiltration Characteristics in Alzheimer’s Disease

Wang

2021

Journal of Healthcare Engineering

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“…The repeatability and reproducibility of the test method should also be checked. Recently, the ultrasensitive immunoassay technique (single-molecule array, Simoa) has achieved great progress in the sensitive detection of plasma A β and p-tau ( Chatterjee et al, 2021 ). However, early and effective diagnosis of AD remains a challenge due to the complexity of AD pathogenesis, which leads to production of several related biomarkers and lack of reproducibility.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Recent Advances in the Application Peptide and Peptoid in Diagnosis Biomarkers of Alzheimer’s Disease in Blood

Guo

Wang

2021

Front. Mol. Neurosci.

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Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases with irreversible damage of the brain and a continuous pathophysiological process. Early detection and accurate diagnosis are essential for the early intervention of AD. Precise detection of blood biomarkers related to AD could provide a shortcut to identifying early-stage patients before symptoms. In recent years, targeting peptides or peptoids have been chosen as recognition elements in nano-sensors or fluorescence detection to increase the targeting specificity, while peptide-based probes were also developed considering their specific advantages. Peptide-based sensors and probes have been developed according to different strategies, such as natural receptors, high-throughput screening, or artificial design for AD detection. This review will briefly summarize the recent developments and trends of AD diagnosis platforms based on peptide and peptoid as recognition elements and provide insights into the application of peptide and peptoid with different sources and characteristics in the diagnosis of AD biomarkers.

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“…Most p‐tau assays target tau phosphorylated at T181 (p‐tau181), yet tau hyperphosphorylation in AD involves several phosphorylation sites and recently two additional p‐tau species, p‐tau217 and p‐tau231, have gained increased attention 7 . While some studies reported comparable performances, 8–10 others suggested earlier elevations of p‐tau217 and p‐tau231 as well as slightly better performances to detect asymptomatic Aβ pathology relative to p‐tau181 6,10–13 . However, a limitation of these studies is the use of the antibody AT270 for plasma p‐tau181 quantification, which cross‐reacts with p‐tau175, thus limiting assay specificity 14 .…”

Section: Introductionmentioning

confidence: 99%

Phospho‐specific plasma p‐tau181 assay detects clinical as well as asymptomatic Alzheimer's disease

Meyer

Vanbrabant²,

Schaeverbeke

et al. 2022

Ann Clin Transl Neurol

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Objective Plasma phosphorylated‐tau‐181 (p‐tau181) reliably detects clinical Alzheimer's disease (AD) as well as asymptomatic amyloid‐β (Aβ) pathology, but is consistently quantified with assays using antibody AT270, which cross‐reacts with p‐tau175. This study investigates two novel phospho‐specific assays for plasma p‐tau181 and p‐tau231 in clinical and asymptomatic AD. Methods Plasma p‐tau species were quantified with Simoa in 44 AD patients, 40 spouse controls and an independent cohort of 151 cognitively unimpaired (CU) elderly who underwent Aβ‐PET. Simoa plasma Aβ42 measurements were available in a CU subset (N = 69). Receiver operating characteristics and Aβ‐PET associations were used to evaluate biomarker validity. Results The novel plasma p‐tau181 and p‐tau231 assays did not show cross‐reactivity. Plasma p‐tau181 accurately detected clinical AD (area under the curve (AUC) = 0.98, 95% CI 0.95–1.00) as well as asymptomatic Aβ pathology (AUC = 0.84, 95% CI 0.76–0.92), while plasma p‐tau231 did not (AUC = 0.74, 95% CI 0.63–0.85 and 0.61, 95% CI 0.52–0.71, respectively). Plasma p‐tau181, but not p‐tau231, detected asymptomatic Aβ pathology more accurately than age, sex and APOE combined (AUC = 0.64). In asymptomatic elderly, correlations between plasma p‐tau181 and Aβ pathology were observed throughout the cerebral cortex (ρ = 0.40, p < 0.0001), with focal associations within AD‐vulnerable regions, particularly the precuneus. The plasma Aβ42/p‐tau181 ratio did not reflect asymptomatic Aβ pathology better than p‐tau181 alone. Interpretation The novel plasma p‐tau181 assay is an accurate tool to detect clinical as well as asymptomatic AD and provides a phospho‐specific alternative to currently employed immunoassays.

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Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease

Cited by 138 publications

References 44 publications

Identification of Hub Genes and Immune Cell Infiltration Characteristics in Alzheimer’s Disease

Identification of Hub Genes and Immune Cell Infiltration Characteristics in Alzheimer’s Disease

Recent Advances in the Application Peptide and Peptoid in Diagnosis Biomarkers of Alzheimer’s Disease in Blood

Phospho‐specific plasma p‐tau181 assay detects clinical as well as asymptomatic Alzheimer's disease

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