Eleanor Drummond

The University of Sydney · Brain and Mind Research Institute

Background APOE polymorphism is the major genetic risk factor for sporadic Alzheimer’s disease (AD), characterized by the abnormal accumulation of β‐amyloid (Aβ) and phosphorylated Tau (pTau). Although the various ApoE isoforms are known mostly to differentially modulate Aβ aggregation and clearance, recent data support an influence of APOE genotyp...

INTRODUCTION Alzheimer's disease (AD) and primary age‐related tauopathy (PART) both harbor 3R/4R hyperphosphorylated‐tau (p‐tau)‐positive neurofibrillary tangles (NFTs) but differ in the spatial p‐tau development in the hippocampus. METHODS Using Nanostring GeoMx Digital Spatial Profiling, we compared protein expression within hippocampal subregio...

Proteomic studies of human Alzheimer’s disease brain tissue have potential to identify protein changes that drive disease, and to identify new drug targets. Here, we analyse 38 published Alzheimer’s disease proteomic studies, generating a map of protein changes in human brain tissue across thirteen brain regions, three disease stages (preclinical A...

Tauopathies, diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of frontotemporal dementia, make up the vast majority of dementia cases. Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments, ongoing progress is required to ensure these are effecti...

Proteomic studies of human Alzheimer’s disease brain tissue have exceptional potential to identify protein changes that drive disease and to identify new drug targets. Here, we detail a combined analysis of 38 published Alzheimer’s disease proteomic studies, generating a comprehensive map of protein changes in human brain tissue across thirteen bra...

Phosphorylated tau is the main protein present in neurofibrillary tangles, the presence of which is a key neuropathological hallmark of Alzheimer’s disease (AD). The toxic effects of phosphorylated tau are likely mediated by interacting proteins; however, methods to identify these interacting proteins comprehensively in human brain tissue are limit...

Pathological tau aggregation is a primary neuropathological feature of many neurodegenerative diseases. Intriguingly, despite the common presence of tau aggregates in these diseases the affected brain regions, clinical symptoms, and morphology, conformation, and isoform ratio present in tau aggregates varies widely. The tau-mediated disease mechani...

Amyloid plaques contain many proteins in addition to beta amyloid (Aβ). Previous studies examining plaque-associated proteins have shown these additional proteins are important; they provide insight into the factors that drive amyloid plaque development and are potential biomarkers or therapeutic targets for Alzheimer’s disease (AD). The aim of thi...

Amyloid plaques contain many proteins in addition to beta amyloid (Aβ). Previous studies examining plaque-associated proteins have shown these additional proteins are important; they provide insight into the factors that drive amyloid plaque development and are potential biomarkers or therapeutic targets for Alzheimer’s disease (AD). The aim of thi...

Objective To identify the molecular signaling pathways underlying sudden unexpected death in epilepsy (SUDEP) and high-risk SUDEP compared to epilepsy control patients. Methods For proteomics analyses, we evaluated the hippocampus and frontal cortex from microdissected post-mortem brain tissue of 12 SUDEP and 14 non-SUDEP epilepsy patients. For tr...

Epilepsy is a common neurological disorder affecting over 70 million people worldwide, with a high rate of pharmaco-resistance, diverse comorbidities including progressive cognitive and behavioral disorders, and increased mortality from direct (e.g., sudden unexpected death in epilepsy, accidents, drowning) or indirect effects of seizures and thera...

Background Accumulation of phosphorylated tau (pTau) is a key pathological feature of Alzheimer’s disease (AD). pTau accumulation causes synaptic impairment, neuronal dysfunction and formation of neurofibrillary tangles (NFTs). The pathological actions of pTau are mediated by surrounding neuronal proteins, however our knowledge of the specific prot...

Background Alzheimer's Disease (AD) patients are more likely to experience epileptic seizures, and cognitive impairment is a frequent comorbidity in patients with epilepsy. Emerging findings indicate a common link between epilepsy and AD, however our understanding of the pathological changes shared between these two diseases is limited. Therefore,...

Background Amyloid plaques contain many proteins in addition to beta amyloid (Aß). Previous studies examining individual plaque‐associated proteins have shown that the presence of these proteins is important: they provide insight into Alzheimer’s disease (AD) pathogenesis, and they are potential biomarkers and/or therapeutic targets for AD. However...

Accumulation of phosphorylated tau is a key pathological feature of Alzheimer’s disease. Phosphorylated tau accumulation causes synaptic impairment, neuronal dysfunction and formation of neurofibrillary tangles. The pathological actions of phosphorylated tau are mediated by surrounding neuronal proteins; however, a comprehensive understanding of th...

Sudden unexpected death in epilepsy (SUDEP) is the leading type of epilepsy-related death. Severely depressed brain activity in these cases may impair respiration, arousal, and protective reflexes, occurring as a prolonged postictal generalized EEG suppression (PGES) and resulting in a high-risk for SUDEP. In autopsy hippocampus and cortex, we obse...

Epilepsy is a common neurological disorder affecting over 70 million people worldwide, with a high rate of pharmaco-resistance, diverse comorbidities including progressive cognitive and behavioral disorders, and increased mortality from direct (e.g., Sudden Unexpected Death in Epilepsy [SUDEP], accidents, drowning) or indirect effects of seizures a...

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that is growing in prevalence globally. It is the only major cause of death without any effective pharmacological means to treat or slow progression. Inheritance of the ε4 allele of the Apolipoprotein (APO) E gene is the strongest genetic risk factor for late-onset AD. The interac...

We recently identified Secernin-1 (SCRN1) as a novel amyloid plaque associated protein using localized proteomics. Immunohistochemistry studies confirmed that SCRN1 was present in plaque-associated dystrophic neurites and also revealed distinct and abundant co-localization with neurofibrillary tangles (NFTs). Little is known about the physiological...

ABSTRACT Our current understanding of the molecular changes that drive Alzheimer’s disease (AD) pathogenesis is incomplete. Unbiased, mass spectrometry-based proteomic studies provide an efficient and comprehensive way to quantitatively examine thousands of proteins at once using microscopic amounts of human brain tissue. Recently, the number of pr...

There are growing genetic, transcriptomic and proteomic data pointing to the complexity of Alzheimer's disease (AD) pathogenesis. Unbiased "omics" approaches are essential for the future development of effective AD research, which will need to be combined and personalized, given that multiple distinct pathways can drive AD pathology. It is essentia...

Introduction: Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by protein aggregates of amyloid β (Aβ) and tau. These proteins have normal physiological functions, but in AD they undergo a conformational change and aggregate as toxic oligomeric and fibrillar species with a high β-sheet content. Areas covered: Active...

There is growing genetic and proteomic data highlighting the complexity of Alzheimer's disease (AD) pathogenesis. Greater use of unbiased "omics" approaches is being increasingly recognized as essential for the future development of effective AD research, that need to better reflect the multiple distinct pathway abnormalities that can drive AD path...

Background Oligomeric forms of amyloid-β (Aβ) and tau are increasing being recognized as key toxins in the pathogenesis of Alzheimer’s disease (AD). Methods We developed a novel monoclonal antibody (mAb), GW-23B7, that recognizes β-sheet secondary structure on pathological oligomers of neurodegenerative diseases. ResultsThe pentameric immunoglobuli...

Here, we describe a new method that allows localized proteomics of amyloid plaques and neurofibrillary tangles (NFTs), which are the two pathological hallmarks of Alzheimer’s disease (AD). Amyloid plaques and NFTs are visualized using immunohistochemistry and microdissected from archived, formalin-fixed paraffin-embedded (FFPE) human tissue samples...

Localized proteomics of specific cell populations will greatly aid understanding of the complex etiology of neurodegenerative diseases. The use of proteomics offers considerable advantages over traditional protein detection techniques and is likely to be particularly useful for studying neurodegenerative diseases, as selective vulnerability of spec...

Rapidly progressive Alzheimer’s disease (rpAD) is a particularly aggressive form of Alzheimer’s disease, with a median survival time of 7–10 months after diagnosis. Why these patients have such a rapid progression of Alzheimer’s disease is currently unknown. To further understand pathological differences between rpAD and typical sporadic Alzheimer’...

Studies in vivo and in vitro have suggested that the mechanism underlying Alzheimer’s disease (AD) neuropathogenesis is initiated by an interaction between the cellular prion protein (PrPC) and amyloid-β oligomers (Aβo). This PrPC-Aβo complex activates Fyn kinase which, in turn, hyperphosphorylates tau (P-Tau) resulting in synaptic dysfunction, neu...

Experimental models of Alzheimer’s disease (AD) are critical to gaining a better understanding of pathogenesis and to assess the potential of novel therapeutic approaches. The most commonly used experimental animal models are transgenic mice that overexpress human genes associated with familial AD (FAD) that result in the formation of amyloid plaqu...

Purpose: There is considerable variability in the extent and nature of the glial response to injury and neurodegeneration. Transplantation of fetal cortical tissue onto the brain of neonatal host rats or mice results in region-specific changes dependent on where the fetal tissue is placed. These changes include chronic astrocytic and microglial gl...

The vast majority of human tissue specimens are formalin-fixed, paraffin embedded (FFPE) archival samples, making this type of tissue a potential gold mine for medical research. It is now accepted that proteomics can be done using FFPE tissue and can generate similar results as snap-frozen tissue. However, the current methodology requires a large a...

Alzheimer's disease (AD) is the most common form of dementia worldwide. It is characterized by an imbalance between the production and clearance of amyloid β (Aβ) and tau proteins. In AD these normal proteins accumulate, leading to aggregation and a conformational change forming oligomeric and fibrillary species with a high β-sheet content. Active...

Background: The sympathetic nervous system may play an important role in certain forms of chronic pain. The main aim of this study was to determine whether functional blockade of α1 -adrenoceptors would alter sensitivity to cutaneous stimulation in patients with complex regional pain syndrome (CRPS). Methods and results: In an initial study, hig...

Aggregation of amyloid β-peptide (Aβ) is implicated in the pathology of Alzheimer's disease (AD), with the soluble, Aβ oligomeric species thought to be the critical pathological species. Identification and characterization of intermediate species formed during the aggregation process is crucial to the understanding of the mechanisms by which oligom...

Stimulation of α1-adrenoceptors evokes inflammatory cytokine production, boosts neurogenic inflammation and pain, and influences cellular migration and proliferation. As expression of α1-adrenoceptors increases on dermal nerves and keratinocytes after peripheral nerve injury, the aim of this study was to determine whether another form of tissue inj...

Background In a small radioligand-binding study of cutaneous α1-adrenoceptors in complex regional pain syndrome (CRPS), signal intensity was greater in the CRPS-affected limb than in controls. However, it was not possible to localize heightened expression of α1-adrenoceptors to nerves, sweat glands, blood vessels, or keratinocytes using this techni...

In certain forms of nerve injury and inflammation, noradrenaline augments pain via actions on up-regulated α1-adrenoceptors (α1-AR). The aim of this study was to use immunohistochemistry to examine α1-AR expression on peripheral neurons, cutaneous blood vessels and keratinocytes after distal tibia fracture and cast immobilization, a model of comple...

Purpose: In adult rats, intravitreal injections of the Rho-GTPase inhibitor C3 transferase (BA-210), or a cocktail of recombinant ciliary neurotrophic factor (CNTF) and a cyclic AMP analogue (CPTcAMP), increase retinal ganglion cell (RGC) survival and axonal regeneration. Here we examined whether these treatments also affect the dendritic architec...

After peripheral nerve injury, nociceptive afferents acquire an abnormal excitability to adrenergic agents, possibly due to an enhanced expression of α1-adrenoceptors (α1-AR) on these nerve fibres. To investigate this in the present study, changes in α1-AR expression on nerve fibres in the skin and sciatic nerve trunk were assessed using immunohist...

Alpha1-adrenoceptor expression on nociceptors may play an important role in sympathetic-sensory coupling in certain neuropathic pain syndromes. The aim of this study was to determine whether α1-adrenoceptor expression was up-regulated on surviving peptidergic, non-peptidergic and myelinated nerve fiber populations in the skin after chronic constric...

Accumulation of beta amyloid (Aβ) in the brain is a primary feature of Alzheimer's disease (AD) but the exact molecular mechanisms by which Aβ exerts its toxic actions are not yet entirely clear. We documented pathological changes 3 and 6 months after localised injection of recombinant, bi-cistronic adeno-associated viral vectors (rAAV2) expressing...

Age-related depletion of estrogens and androgens is associated with an increase in Alzheimer's disease (AD) brain pathology and diminished cognitive function. Here we investigated AD-associated molecular and cellular changes in brains of aged hypogonadal (hpg) male and female mice. hpg Mice have a spontaneous, inactivating genetic mutation in the G...

Recombinant adeno-associated viral (rAAV) vectors can be used to introduce neurotrophic genes into injured CNS neurons, promoting survival and axonal regeneration. Gene therapy holds much promise for the treatment of neurotrauma and neurodegenerative diseases; however, neurotrophic factors are known to alter dendritic architecture, and thus we set...

To discuss the relationship between androgens, cognition and Alzheimer's disease. It has been found that low circulating levels of androgens are a risk factor for Alzheimer's disease. Decreased circulating androgens are also associated with declining cognitive performance, particularly in memory-related tasks. Conversely, androgen supplementation t...

We here describe various approaches using GFP that are being used in the morphological and functional analysis of specific cell types in the normal and injured central nervous system. Incorporation of GFP into viral vectors allows phenotypic characterization of transduced cells and can be used to label their axons and terminal projections. Characte...