Aaron Z. Wagen
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View article: TDP-43 loss of function drives aberrant splicing in Parkinson’s disease
TDP-43 loss of function drives aberrant splicing in Parkinson’s disease Open
Introductory paragraph While mRNA splicing dysregulation is a well-established contributor to neurodegeneration in disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), its role in Parkinson’s disease (PD…
View article: Independent Generation of Amyloid-β via Novel<i>APP</i>Transcripts
Independent Generation of Amyloid-β via Novel<i>APP</i>Transcripts Open
The amyloid precursor protein ( APP ) is processed by multiple enzymes to generate biologically active peptides, including amyloid-β (Aβ), which aggregates to form the hallmark pathology of Alzheimer’s disease (AD). Aβ is produced through …
View article: Astrocytic RNA editing regulates the host immune response to alpha-synuclein
Astrocytic RNA editing regulates the host immune response to alpha-synuclein Open
RNA editing is a posttranscriptional mechanism that targets changes in RNA transcripts to modulate innate immune responses. We report the role of astrocyte-specific, ADAR1-mediated RNA editing in neuroinflammation in Parkinson’s disease (P…
View article: Accelerated midlife epigenetic age associates with poor later life brain health in the 1946 British Birth Cohort
Accelerated midlife epigenetic age associates with poor later life brain health in the 1946 British Birth Cohort Open
Background Accelerated epigenetic ageing has been associated with various age‐related health outcomes, but its relevance for dementia risk prediction is unclear. We investigated whether accelerated midlife epigenetic age associates with po…
View article: Ancestry-specific gene expression in peripheral monocytes mediates risk of neurodegenerative disease
Ancestry-specific gene expression in peripheral monocytes mediates risk of neurodegenerative disease Open
It is hypothesised that peripheral immune states responding to regional environmental triggers contribute to central neurodegeneration. Region-specific genetic selection pressures require this hypothesis to be assessed in an ancestry speci…
View article: RNA editing is a molecular clock in unmodified human cells
RNA editing is a molecular clock in unmodified human cells Open
Despite major advances in spatial RNA sequencing, the ability to extract temporal information in RNA sequencing experiments is still limited. Here, we describe Transcriptome Timestamping (T2), a system which harnesses naturally occurring A…
View article: GLP1 receptor agonism ameliorates Parkinson’s disease through modulation of neuronal insulin signalling and glial suppression
GLP1 receptor agonism ameliorates Parkinson’s disease through modulation of neuronal insulin signalling and glial suppression Open
Neuronal insulin resistance is linked to the pathogenesis of Parkinson’s disease through unclear, but potentially targetable, mechanisms. We delineated neuronal and glial mechanisms of insulin resistance and glucagon-like 1 peptide (GLP-1)…
View article: Astrocytic RNA editing regulates the host immune response to alpha-synuclein
Astrocytic RNA editing regulates the host immune response to alpha-synuclein Open
RNA editing is a post transcriptional mechanism that targets changes in RNA transcripts to modulate innate immune responses. We report the role of astrocyte specific, ADAR1 mediated RNA editing in neuroinflammation in Parkinson’s disease. …
View article: Rates of cortical thinning in Alzheimer’s disease signature regions associate with vascular burden but not with β-amyloid status in cognitively normal adults at age 70
Rates of cortical thinning in Alzheimer’s disease signature regions associate with vascular burden but not with β-amyloid status in cognitively normal adults at age 70 Open
Background Consistent patterns of reduced cortical thickness have been identified in early Alzheimer’s disease (AD). However, the pathological factors that influence rates of cortical thinning within these AD signature regions remain uncle…
View article: Genome‐Wide Association Study of Pericardial Fat Area in 28 161 UK Biobank Participants
Genome‐Wide Association Study of Pericardial Fat Area in 28 161 UK Biobank Participants Open
BACKGROUND Pericardial adipose tissue (PAT) is the visceral adipose tissue compartment surrounding the heart. Experimental and observational research has suggested that greater PAT deposition might mediate cardiovascular disease, independe…
View article: Associations between peripheral hearing ability at age 70, brain atrophy and cognitive decline in adults born in the same week of 1946
Associations between peripheral hearing ability at age 70, brain atrophy and cognitive decline in adults born in the same week of 1946 Open
Background Peripheral hearing impairment has been proposed as a risk factor for dementia. However, the relationship between hearing ability, neurodegeneration and cognitive decline, and the extent to which pathological processes associated…
View article: Longitudinal trajectories of self‐reported subjective cognitive decline in relation to objective cognitive performance in a population‐based cohort
Longitudinal trajectories of self‐reported subjective cognitive decline in relation to objective cognitive performance in a population‐based cohort Open
Background Subjective Cognitive Decline (SCD) may represent the onset of cognitive decline before impairment on standard cognitive tests occurs (Jessen et al., 2014). Previous cross‐sectional studies were shown to have limited ability to c…
View article: Author Correction: Local genetic correlations exist among neurodegenerative and neuropsychiatric diseases
Author Correction: Local genetic correlations exist among neurodegenerative and neuropsychiatric diseases Open
View article: Local genetic correlations exist among neurodegenerative and neuropsychiatric diseases
Local genetic correlations exist among neurodegenerative and neuropsychiatric diseases Open
Genetic correlation ( $$r_g$$ ) between traits can offer valuable insight into underlying shared biological mechanisms. Neurodegenerative diseases overlap neuropathologically and often manifest comorbid neuropsychiatric symptoms. How…
View article: Neuroimaging, clinical and life course correlates of normal-appearing white matter integrity in 70-year-olds
Neuroimaging, clinical and life course correlates of normal-appearing white matter integrity in 70-year-olds Open
We investigate associations between normal-appearing white matter microstructural integrity in cognitively normal ∼70-year-olds and concurrently measured brain health and cognition, demographics, genetics and life course cardiovascular hea…
View article: Rates of cortical thinning in Alzheimer’s disease signature regions: pathological influences and cognitive consequences in members of the 1946 British birth cohort
Rates of cortical thinning in Alzheimer’s disease signature regions: pathological influences and cognitive consequences in members of the 1946 British birth cohort Open
Background Consistent patterns of reduced cortical thickness (so‐called signature regions) have been identified in early Alzheimer’s disease (AD), including in the pre‐dementia stages, but studies investigating the pathological underpinnin…
View article: Life course, genetic, and neuropathological associations with brain age in the 1946 British Birth Cohort: a population-based study
Life course, genetic, and neuropathological associations with brain age in the 1946 British Birth Cohort: a population-based study Open
View article: Local genetic correlations exist among neurodegenerative and neuropsychiatric diseases
Local genetic correlations exist among neurodegenerative and neuropsychiatric diseases Open
Genetic correlation ( r g ) between traits can offer valuable insight into underlying shared biological mechanisms. Neurodegenerative diseases overlap neuropathologically and often manifest comorbid neuropsychiatric symptoms. However, glob…
View article: Cerebral amyloid and white matter hyperintensity volume are independently associated with rates of cerebral atrophy in Insight 46, a sub‐study of the 1946 British birth cohort
Cerebral amyloid and white matter hyperintensity volume are independently associated with rates of cerebral atrophy in Insight 46, a sub‐study of the 1946 British birth cohort Open
Background Alzheimer’s (AD) and cerebrovascular disease are common causes of cognitive impairment in later life and often co‐exist. Understanding how AD and vascular pathologies act independently or together to influence neurodegeneration …
View article: Serum neurofilament light and whole brain volume associate with machine‐learning derived brain‐predicted age in the British 1946 birth cohort
Serum neurofilament light and whole brain volume associate with machine‐learning derived brain‐predicted age in the British 1946 birth cohort Open
Background Age is the biggest risk factor for dementia, yet human brains do not age uniformly. The British 1946 birth cohort, the world’s longest continuously running birth cohort, provides a unique opportunity to assess these variations i…
View article: Accelerated forgetting is sensitive to β‐amyloid pathology and cerebral atrophy in cognitively normal 72‐year‐olds
Accelerated forgetting is sensitive to β‐amyloid pathology and cerebral atrophy in cognitively normal 72‐year‐olds Open
Background Accelerated Forgetting (AF) is the phenomenon whereby material is retained normally over short intervals (minutes or hours) but forgotten abnormally rapidly over longer periods (days or weeks). AF has been observed in presymptom…
View article: Biochemically-defined pools of amyloid-β in sporadic Alzheimer’s disease: correlation with amyloid PET
Biochemically-defined pools of amyloid-β in sporadic Alzheimer’s disease: correlation with amyloid PET Open
We fractionated frontal cortical grey matter from human Alzheimer's disease and control subjects into four biochemically defined pools that represent four distinct compartments: soluble/cytosolic, peripheral membrane/vesicular cargo, integ…
View article: Applying matrix assisted laser desorption-ionization mass spectrometry to identify and quantify isoforms of amyloid beta in human brain
Applying matrix assisted laser desorption-ionization mass spectrometry to identify and quantify isoforms of amyloid beta in human brain Open
View article: Urinary tract infections due to extended-spectrum beta-lactamase-producing Gram-negative bacteria: identification of risk factors and outcome predictors in an Australian tertiary referral hospital
Urinary tract infections due to extended-spectrum beta-lactamase-producing Gram-negative bacteria: identification of risk factors and outcome predictors in an Australian tertiary referral hospital Open