Nucleic acid liquid biopsies in Alzheimer's disease: current state, challenges, and opportunities

Soelter, Tabea M.; Whitlock, Jordan; Williams, Avery S.; Hardigan, Andrew A.; Lasseigne, Brittany N.

doi:10.1016/j.heliyon.2022.e09239

Cited by 6 publications

(3 citation statements)

References 133 publications

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“…Priming could improve detection of microbial cfDNA during early or deep-seated infections ( 70 ), where diagnosis is critical for therapy selection but remains challenging. Liquid biopsy–based applications in cardiovascular disease and Alzheimer’s disease are other areas where the low abundance of cfDNA is a limitation, and where priming agents may be beneficial ( 71 , 72 ). Deeper characterization of the effect of priming on other aspects of cfDNA, such as epigenetics and fragmentomics, could reveal further insights into cfDNA biology and motivate other applications.…”

Section: Discussionmentioning

confidence: 99%

Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies

Martin-Alonso,

Tabrizi,

Xiong

et al. 2024

Science

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Liquid biopsies enable early detection and monitoring of diseases such as cancer, but their sensitivity remains limited by the scarcity of analytes such as cell-free DNA (cfDNA) in blood. Improvements to sensitivity have primarily relied on enhancing sequencing technology ex vivo. We sought to transiently augment the level of circulating tumor DNA (ctDNA) in a blood draw by attenuating its clearance in vivo. We report two intravenous priming agents given 1 to 2 hours before a blood draw to recover more ctDNA. Our priming agents consist of nanoparticles that act on the cells responsible for cfDNA clearance and DNA-binding antibodies that protect cfDNA. In tumor-bearing mice, they greatly increase the recovery of ctDNA and improve the sensitivity for detecting small tumors.

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Section: Discussionmentioning

confidence: 99%

Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies

Martin-Alonso,

Tabrizi,

Xiong

et al. 2024

Science

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“…Additional recent liquid biopsy developments relating to Alzheimer’s disease, 126 , 143 , 144 and MCI 145 are reviewed elsewhere.…”

Section: Recent Developments and Applications Of Cfdna-based Liquid B...mentioning

confidence: 99%

Cell-free DNA-based liquid biopsies in neurology

Gaitsch

Franklin²,

Reich

2022

Brain

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This article reviews recent developments in the application of cell-free DNA-based liquid biopsies to neurological diseases. Over the past few decades, an explosion of interest in the use of accessible biofluids to identify and track molecular disease has revolutionized the fields of oncology, prenatal medicine, and others. More recently, technological advances in signal detection have allowed for informative analysis of biofluids that are typically sparse in cells and other circulating components, such as cerebrospinal fluid. In parallel, advancements in epigenetic profiling have allowed for novel applications of liquid biopsies to diseases without characteristic mutational profiles, including many degenerative, autoimmune, inflammatory, ischaemic, and infectious disorders. These events have paved the way for a wide array of neurological conditions to benefit from enhanced diagnostic, prognostic, and treatment abilities through the use of liquid biomarkers: a “liquid biopsy” approach. This review includes an overview of types of liquid biopsy targets with a focus on circulating cell-free DNA, methods used to identify and probe potential liquid biomarkers, and recent applications of such biomarkers to a variety of complex neurological conditions including CNS tumours, stroke, traumatic brain injury, Alzheimer’s disease, epilepsy, multiple sclerosis, and neuroinfectious disease. Finally, the challenges of translating liquid biopsies to use in clinical neurology settings—and the opportunities for improvement in disease management that such translation may provide—are discussed.

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“…14 However, most patients have sporadic or late-onset AD, where the genetic causes are not fully understood. 15 One approach to early AD diagnosis involves detecting nucleic acids and proteins like amyloid-β in cerebrospinal fluid and blood through liquid biopsies (reviewed in [16][17][18] ). However, the blood-brain barrier impacts detection sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of altered cell-cell communication between glia and neurons in the hippocampus of 3xTg-AD mice at two time points

Soelter,

Howton,

Wilk

et al. 2024

Preprint

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Alzheimer's disease (AD) is the most common form of dementia and is characterized by progressive memory loss and cognitive decline, affecting behavior, speech, and motor abilities. The neuropathology of AD includes the formation of extracellular amyloid-β ; plaque and intracellular neurofibrillary tangles of phosphorylated tau, along with neuronal loss. While neuronal loss is an AD hallmark, cell-cell communication between neuronal and non-neuronal cell populations maintains neuronal health and brain homeostasis. To study changes in cell-cell communication during disease progression, we performed snRNA-sequencing of the hippocampus from female 3xTg-AD and wild-type littermates at 6 and 12 months. We inferred differential cell-cell communication between 3xTg-AD and wild-type mice across time points and between senders (astrocytes, microglia, oligodendrocytes, and OPCs) and receivers (excitatory and inhibitory neurons) of interest. We also assessed the downstream effects of altered glia-neuron communication using pseudobulk differential gene expression, functional enrichment, and gene regulatory analyses. We found that glia-neuron communication is increasingly dysregulated in 12-month 3xTg-AD mice. We also identified 23 AD-associated ligand-receptor pairs that are upregulated in the 12-month-old 3xTg-AD hippocampus. Our results suggest increased AD association of interactions originating from microglia. Signaling mediators were not significantly differentially expressed but showed altered gene regulation and TF activity. Our findings indicate that altered glia-neuron communication is increasingly dysregulated and affects the gene regulatory mechanisms in neurons of 12-month-old 3xTg-AD mice.

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Nucleic acid liquid biopsies in Alzheimer's disease: current state, challenges, and opportunities

Cited by 6 publications

References 133 publications

Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies

Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies

Cell-free DNA-based liquid biopsies in neurology

Evaluation of altered cell-cell communication between glia and neurons in the hippocampus of 3xTg-AD mice at two time points

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