Declan King
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View article: Evidence for trans-synaptic propagation of oligomeric tau in human progressive supranuclear palsy
Evidence for trans-synaptic propagation of oligomeric tau in human progressive supranuclear palsy Open
View article: Divergent actions of physiological and pathological amyloid-β on synapses in live human brain slice cultures
Divergent actions of physiological and pathological amyloid-β on synapses in live human brain slice cultures Open
View article: Studying protein interactions in human synapses using array tomography
Studying protein interactions in human synapses using array tomography Open
Background Synapse loss represents the closest correlate of cognitive decline in Alzheimer’s Disease (AD). Standard microscopy, due to increased diffraction of light with tissue depth, imposes a limit on axial resolution extending to ∼ 700…
View article: Microglia determine ß-amyloid plaque burden but are non-essential for downstream pathology
Microglia determine ß-amyloid plaque burden but are non-essential for downstream pathology Open
Evidence points to a role for microglia in Alzheimer’s disease (AD) risk, although their position in the pathological cascade is incompletely understood, prompting us to generate a model of ß-amyloidopathy lacking microglia. We find eviden…
View article: Synaptic gene expression changes in frontotemporal dementia due to the <i>MAPT</i> 10 + 16 mutation
Synaptic gene expression changes in frontotemporal dementia due to the <i>MAPT</i> 10 + 16 mutation Open
Aims Mutations in the MAPT gene encoding tau protein can cause autosomal dominant neurodegenerative tauopathies including frontotemporal dementia (often with Parkinsonism). In Alzheimer's disease, the most common tauopathy, synapse loss is…
View article: Synaptic gene expression changes in frontotemporal dementia due to the<i>MAPT</i>10+16 mutation
Synaptic gene expression changes in frontotemporal dementia due to the<i>MAPT</i>10+16 mutation Open
Mutations in the MAPT gene encoding tau protein can cause autosomal dominant neurodegenerative tauopathies including frontotemporal dementia (often with Parkinsonism). In Alzheimer’s disease, the most common tauopathy, synapse loss is the …
View article: Transmembrane protein 97 is a potential synaptic amyloid beta receptor in human Alzheimer’s disease
Transmembrane protein 97 is a potential synaptic amyloid beta receptor in human Alzheimer’s disease Open
Synapse loss correlates with cognitive decline in Alzheimer’s disease, and soluble oligomeric amyloid beta (Aβ) is implicated in synaptic dysfunction and loss. An important knowledge gap is the lack of understanding of how Aβ leads to syna…
View article: A study to determine the mechanisms underlying changes in synaptic vesicle glycoprotein 2A density in Alzheimer’s disease
A study to determine the mechanisms underlying changes in synaptic vesicle glycoprotein 2A density in Alzheimer’s disease Open
Background Synaptic vesicle glycoprotein 2A (SV2A) is a transmembrane synaptic vesicle protein that regulates vesicle exocytosis and neurotransmitter release. Positron emission tomography (PET) studies reveal that the levels of SV2A are de…
View article: Human astrocytes and microglia show augmented ingestion of synapses in Alzheimer’s disease via MFG-E8
Human astrocytes and microglia show augmented ingestion of synapses in Alzheimer’s disease via MFG-E8 Open
Synapse loss correlates with cognitive decline in Alzheimer's disease (AD). Data from mouse models suggests microglia are important for synapse degeneration, but direct human evidence for any glial involvement in synapse removal in human A…
View article: Neurogranin in Alzheimer's disease and ageing: A human post-mortem study
Neurogranin in Alzheimer's disease and ageing: A human post-mortem study Open
Neurogranin (Ng), a post-synaptic protein involved in memory formation, has been investigated as a biomarker in the cerebrospinal fluid (CSF) in Alzheimer's disease (AD) and ageing. CSF Ng levels are elevated in AD relative to healthy cont…
View article: Predictive blood biomarkers and brain changes associated with age-related cognitive decline
Predictive blood biomarkers and brain changes associated with age-related cognitive decline Open
Growing evidence supports the use of plasma levels of tau phosphorylated at threonine 181, amyloid-β, neurofilament light and glial fibrillary acidic protein as promising biomarkers for Alzheimer’s disease. While these blood biomarkers are…
View article: Clinical course in corticobasal syndrome and corticobasal degeneration: implications for diagnosis and management
Clinical course in corticobasal syndrome and corticobasal degeneration: implications for diagnosis and management Open
This scientific commentary relates to ‘Clinical course of pathologically confirmed corticobasal degeneration and corticobasal syndrome’, by Aiba et al. (https://doi.org/10.1093/braincomms/fcad296).
View article: Synaptic resilience is associated with maintained cognition during ageing
Synaptic resilience is associated with maintained cognition during ageing Open
Introduction It remains unclear why age increases risk of Alzheimer's disease and why some people experience age‐related cognitive decline in the absence of dementia. Here we test the hypothesis that resilience to molecular changes in syna…
View article: Evidence for trans-synaptic propagation of oligomeric tau in Progressive Supranuclear Palsy
Evidence for trans-synaptic propagation of oligomeric tau in Progressive Supranuclear Palsy Open
In the neurodegenerative disease Progressive Supranuclear Palsy (PSP), tau pathology progresses through the brain in a stereotypical spatiotemporal pattern, and where tau pathology appears, synapses are lost. We tested the hypothesis that …
View article: Synaptic resilience is associated with maintained cognition during ageing
Synaptic resilience is associated with maintained cognition during ageing Open
INTRODUCTION It remains unclear why age increases risk of Alzheimer’s disease and why some people experience age-related cognitive decline in the absence of dementia. Here we test the hypothesis that resilience to molecular changes in syna…
View article: A comparison of blood and brain‐derived ageing and inflammation‐related DNA methylation signatures and their association with microglial burdens
A comparison of blood and brain‐derived ageing and inflammation‐related DNA methylation signatures and their association with microglial burdens Open
Inflammation and ageing‐related DNA methylation patterns in the blood have been linked to a variety of morbidities, including cognitive decline and neurodegenerative disease. However, it is unclear how these blood‐based patterns relate to …
View article: Associations between cerebrospinal fluid markers and cognition in ageing and dementia: A systematic review
Associations between cerebrospinal fluid markers and cognition in ageing and dementia: A systematic review Open
A biomarker associated with cognition in neurodegenerative dementias would aid in the early detection of disease progression, complement clinical staging and act as a surrogate endpoint in clinical trials. The current systematic review eva…
View article: Association between plasma phospho-tau181 and cognitive change from age 73 to 82: Lothian Birth Cohort 1936
Association between plasma phospho-tau181 and cognitive change from age 73 to 82: Lothian Birth Cohort 1936 Open
INTRODUCTION Plasma phospho-tau 181 (p-tau181) is a promising blood biomarker for Alzheimer’s disease. However, its predictive validity for age-related cognitive decline without dementia remains unclear. Several forms of p-tau have been sh…
View article: Review for "Persistent DNA damage alters the neuronal transcriptome suggesting cell cycle dysregulation and altered mitochondrial function"
Review for "Persistent DNA damage alters the neuronal transcriptome suggesting cell cycle dysregulation and altered mitochondrial function" Open
View article: Inhibitory synapse loss and accumulation of amyloid beta in inhibitory presynaptic terminals in Alzheimer's disease
Inhibitory synapse loss and accumulation of amyloid beta in inhibitory presynaptic terminals in Alzheimer's disease Open
Background and purpose Synapse degeneration in Alzheimer's disease (AD) correlates strongly with cognitive decline. There is well‐established excitatory synapse loss in AD with known contributions of pathological amyloid beta (Aβ) to excit…
View article: Review for "Persistent DNA damage alters the neuronal transcriptome suggesting cell cycle dysregulation and altered mitochondrial function"
Review for "Persistent DNA damage alters the neuronal transcriptome suggesting cell cycle dysregulation and altered mitochondrial function" Open
View article: Microarray profiling emphasizes transcriptomic differences between hippocampal <i>in vivo</i> tissue and <i>in vitro</i> cultures
Microarray profiling emphasizes transcriptomic differences between hippocampal <i>in vivo</i> tissue and <i>in vitro</i> cultures Open
Primary hippocampal cell cultures are routinely used as an experimentally accessible model platform for the hippocampus and brain tissue in general. Containing multiple cell types including neurons, astrocytes and microglia in a state that…
View article: Supplementary files supporting the paper "Microarray profiling emphasizes transcriptomic differences between hippocampal in vivo tissue and in vitro cultures"
Supplementary files supporting the paper "Microarray profiling emphasizes transcriptomic differences between hippocampal in vivo tissue and in vitro cultures" Open
Differential expression was performed using the R package "limma" (R package version 3.44.3) (Supplementary files 1-4; 1_diff_expr_WT_cell_vs_tissue, 2_diff_expr_101LL_cell_vs_tissue, 3_diff_expr_cell_WT_ vs_101LL, 4_diff_expr_tissue_WT_ v…
View article: Microarray data CEL files supporting the paper "Microarray profiling emphasizes transcriptomic differences between hippocampal in vivo tissue and in vitro cultures"
Microarray data CEL files supporting the paper "Microarray profiling emphasizes transcriptomic differences between hippocampal in vivo tissue and in vitro cultures" Open
Affymetrix microarray processing produced 16 (4 WT cell, 4 101LL cell, 4 WT tissue, 4 101LL tissue) probe cell intensity data (CEL) files. Primary hippocampal cell cultures are routinely used as an experimentally accessible model platform …
View article: A comparison of blood and brain-derived ageing and inflammation-related DNA methylation signatures and their association with microglial burdens
A comparison of blood and brain-derived ageing and inflammation-related DNA methylation signatures and their association with microglial burdens Open
Inflammation and ageing-related DNA methylation patterns in the blood have been linked to a variety of morbidities, including cognitive decline and neurodegenerative disease. However, it is unclear how these blood-based patterns relate to …
View article: High neural activity accelerates the decline of cognitive plasticity with age in Caenorhabditis elegans
High neural activity accelerates the decline of cognitive plasticity with age in Caenorhabditis elegans Open
The ability to learn progressively declines with age. Neural hyperactivity has been implicated in impairing cognitive plasticity with age, but the molecular mechanisms remain elusive. Here, we show that chronic excitation of the Caenorhabd…
View article: Author response: High neural activity accelerates the decline of cognitive plasticity with age in Caenorhabditis elegans
Author response: High neural activity accelerates the decline of cognitive plasticity with age in Caenorhabditis elegans Open
View article: Amyloid Beta and Tau Cooperate to Cause Reversible Behavioral and Transcriptional Deficits in a Model of Alzheimer’s Disease
Amyloid Beta and Tau Cooperate to Cause Reversible Behavioral and Transcriptional Deficits in a Model of Alzheimer’s Disease Open
A key knowledge gap blocking development of effective therapeutics for Alzheimer's disease (AD) is the lack of understanding of how amyloid beta (Aβ) peptide and pathological forms of the tau protein cooperate in causing disease phenotypes…
View article: Comparative profiling of the synaptic proteome from Alzheimer’s disease patients with focus on the APOE genotype
Comparative profiling of the synaptic proteome from Alzheimer’s disease patients with focus on the APOE genotype Open
View article: Human astrocytes and microglia show augmented ingestion of synapses in Alzheimer’s disease via MFG-E8
Human astrocytes and microglia show augmented ingestion of synapses in Alzheimer’s disease via MFG-E8 Open
Summary Synapse loss correlates with cognitive decline in Alzheimer’s disease (AD). Data from mouse models suggests microglia are important for synapse degeneration, but direct human evidence for any glial involvement in synapse removal in…