Publications by authors named "Yvonne S Davidson"

Article Synopsis
  • Corticobasal syndrome is usually linked to common conditions like corticobasal degeneration and Alzheimer's, but this case highlights a rare cause.
  • A 78-year-old woman initially diagnosed with idiopathic Parkinson's disease developed symptoms that led to a revised diagnosis of probable corticobasal syndrome after an MRI showed specific brain atrophy.
  • After her death, post-mortem findings confirmed Pick's disease, demonstrating that it can mimic corticobasal syndrome symptoms, which is important for differential diagnosis.
View Article and Find Full Text PDF
Article Synopsis
  • - The study aimed to explore the relationship between late-life hypertension and Alzheimer's disease (AD) pathology, focusing on individuals over 65 and the effects of antihypertensive medication.
  • - Researchers used self-reported hypertension data and brain assessments from 108 deceased participants, discovering that those with hypertension had lower levels of AD pathology despite no significant cognitive impairment.
  • - The findings imply that late-life hypertension may actually correlate with milder AD pathology, potentially due to factors like reduced blood flow affecting the brain.
View Article and Find Full Text PDF
Article Synopsis
  • Early diagnosis of Alzheimer's disease (AD) through cognitive testing can lead to early intervention, and the Telephone Assessment for Cognitive Screening (TICS) is effective in screening for cognitive impairment, though its ability to signal future AD risk is still being explored.
  • The study investigates the relationship between TICS scores collected over 13 years and the cognitive status of participants at death, alongside their neuropathological indices of AD.
  • Results show that lower TICS scores correlate with cognitive impairment and AD pathology in participants, suggesting that TICS could be a useful tool for identifying those at risk of developing AD long before symptoms appear, potentially allowing for early intervention strategies.
View Article and Find Full Text PDF
Article Synopsis
  • The term "Primary age-related tauopathy" (PART) refers to a condition characterized by the presence of neurofibrillary tangles without associated beta-amyloid pathology, affecting both cognitively normal and impaired individuals.
  • Research indicates that the genetic factor Apolipoprotein E (APOE) ε4 is less common in PART compared to Alzheimer's disease (AD), with APOE ε2 being more prevalent in cases of PART.
  • Findings suggest that individuals with definite PART tend to experience less cognitive impairment than those diagnosed with AD, potentially due to the differing effects of APOE genotypes on Aβ pathology and cognition in older adults.
View Article and Find Full Text PDF
Article Synopsis
  • - The study investigates the link between early depression symptoms and the risk of developing Alzheimer's disease (AD), focusing on how mood changes might indicate a higher likelihood of cognitive impairment later in life.
  • - Researchers analyzed data from a long-term study involving assessments on depression and cognitive status, revealing that higher depression scores were associated with greater cognitive impairment and AD pathology at death.
  • - Findings suggest that early depression symptoms could serve as a potential early diagnostic marker for Alzheimer's by indicating underlying neurological changes related to the disease, even occurring decades before death.
View Article and Find Full Text PDF
Article Synopsis
  • A study explored the connection between genotype and lifespan using data from cognitive health research.
  • The research found that individuals with the 4 allele had a lower chance of reaching 80+ years while remaining cognitively healthy, while 2 allele carriers generally lived longer and stayed cognitively normal.
  • These findings suggest that genotype does impact longevity, particularly in those who are cognitively impaired.
View Article and Find Full Text PDF

Background: The pathological features of Alzheimer's disease (AD) are well described but little is known as to how both neurodegeneration and vascular changes might interact in causing cognitive impairment.

Objective: The present study aims to investigate relationships between vascular and AD pathology in cognitively healthy and cognitively impaired individuals with a particular emphasis on those at intermediate Braak tau stages.

Methods: We investigated the interplay between Braak tau stage and measures of vascular pathology as described by the vascular cognitive impairment neuropathology guidelines (VCING) in 185 brains from the Brains for Dementia Research programme and The University of Manchester Longitudinal Study of Cognition in Healthy Old Age.

View Article and Find Full Text PDF

In the present study, we have characterized and compared individuals whose brains were donated as part of The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age (UoM) with those donated through the Manchester arm of the UK Brains for Dementia Research (BDR) program. The aim of this study was to investigate how differences in study recruitment may affect final pathological composition of cohort studies. The UoM cohort was established as a longitudinal study of aging and cognition whereas the BDR program was established, prima facie, to collect brains from both demented and non-demented individuals for the purpose of building a tissue research resource.

View Article and Find Full Text PDF

Objectives: Head injury with loss of consciousness (HI-LOC) is a common occurrence. Some studies have linked such injuries with an increased risk of Alzheimer disease (AD). However, recent large clinicopathologic studies have failed to find a clear relationship between HI-LOC and the pathological changes associated with AD.

View Article and Find Full Text PDF

While post mortem studies have identified the major cell types and functional systems affected in Alzheimer's disease (AD) the initial sites and molecular characteristics of pathology are still unclear. Because individuals with Down syndrome (DS) (trisomy 21) develop the full pathological changes of AD in a predictable way by the time they reach middle to late age, a study of the brains of such persons at different ages makes an ideal 'model system' in which the sites of earliest onset of pathology can be detected and the subsequent progression of changes be monitored. In the present study we have examined the brains of 56 individuals with DS ranging from new-born to 76 years for the presence of amyloid and tau pathology in key cortical and subcortical regions.

View Article and Find Full Text PDF

The neuropathological changes responsible for cognitive impairment and dementia remain incompletely understood. Longitudinal studies with a brain donation end point allow the opportunity to examine relationships between cognitive status and neuropathology. We report on the first 97 participants coming to autopsy with sufficient clinical information from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age.

View Article and Find Full Text PDF
Article Synopsis
  • - The study investigates amyloid plaque formation and cerebral amyloid angiopathy (CAA) across different groups: APP genetic causes of Alzheimer's disease (AD), older individuals with Down syndrome (DS), and those with sporadic early and late onset AD (sEOAD and sLOAD) to highlight group differences and mechanistic insights.
  • - Findings show that plaque formation is more severe in DS and those with missense APP mutations, while CAA severity is higher in APPdup, missense APP mutations, and DS compared to sEOAD and sLOAD.
  • - The study also explores the role of APOE genotype, revealing that the frequency of the APOE ε4 allele is higher in sEOAD and sLOAD and is
View Article and Find Full Text PDF

A failure of protein degradation may underpin Lewy body disease (LBD) where α-synuclein is assimilated into the pathognomic Lewy bodies and Lewy neurites. We investigated histological alterations in lysosomes and autophagosomes in the substantia nigra (SN) and cingulate gyrus (CG) in 34 patients with LBD employing antibodies against phosphorylated α-synuclein and lysosomal (lysosomal associated membrane proteins 1 and 2 (LAMP-1 and LAMP-2), cathepsin D (CTSD)) and autophagosomal (microtubule-associated protein light chain 3α (LC3A)) proteins. Immunostained sections were qualitatively and semi-quantitatively assessed for the appearance, distribution and intensity of staining.

View Article and Find Full Text PDF

Background: Community- or population-based longitudinal studies of cognitive ability with a brain donation end point offer an opportunity to examine relationships between pathology and cognitive state prior to death. Discriminating the earliest signs of dementing disorders, such as Alzheimer disease (AD), is necessary to undertake early interventions and treatments.

Methods: The neuropathological profile of brains donated from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age, including CERAD (Consortium to Establish a Registry for Alzheimer's Disease) and Braak stage, was assessed by immunohistochemistry.

View Article and Find Full Text PDF

We have employed as 'gold standards' two in-house, well-characterised and validated polyclonal antibodies, C9-L and C9-S, which detect the longer and shorter forms of C9orf72, and have compared seven other commercially available antibodies with these in order to evaluate the utility of the latter as credible tools for the demonstration of C9orf72. C9-L and C9-S antibodies immunostained cytoplasmic 'speckles', and the nuclear membrane, respectively, in cerebellar Purkinje cells of the cerebellum in patients with behavioural variant frontotemporal dementia (bvFTD) with amyotrophic lateral sclerosis (ALS), and in patients with ALS alone. Similar staining was seen in Purkinje cells in healthy control tissues and in other neurodegenerative disorders, and in pyramidal cells of CA4 and dentate gyrus of hippocampus.

View Article and Find Full Text PDF

Frontotemporal Lobar Degeneration (FTLD) encompasses certain related neurodegenerative disorders which alter personality and cognition. Heterogeneous ribonuclear proteins (hnRNPs) maintain RNA metabolism and changes in their function may underpin the pathogenesis of FTLD. Immunostaining for hnRNP E2 was performed on sections of frontal and temporal cortex with hippocampus from 80 patients with FTLD, stratified by pathology into FTLD-tau and FTLD-TDP type A, B and C subtypes, and by genetics into patients with C9orf72 expansions, MAPT or GRN mutations, or those with no known mutation, and on 10 healthy controls.

View Article and Find Full Text PDF

Frontotemporal Lobar Degeneration (FTLD) encompasses certain related neurodegenerative disorders which alter behaviour, personality and language. Heterogeneous ribonuclear proteins (hnRNPs) maintain RNA metabolism and changes in their function may underpin the pathogenesis of FTLD. Immunostaining for hnRNP A1, A2/B1 and A3 was performed on sections of temporal cortex with hippocampus from 61 patients with FTLD, stratified by pathological hallmarks into FTLD-tau and FTLD-TDP type A, B and C subtypes, and by genetics into patients with C9orf72 expansions, MAPT or GRN mutations, or those without known mutation.

View Article and Find Full Text PDF

It has been suggested that patients with motor neurone disease (MND) and those with MND combined with behavioural variant frontotemporal dementia (bvFTD) (ie FTD + MND) or with FTD alone might exist on a continuum based on commonalities of neuropathology and/or genetic risk. Moreover, it has been reported that both a neuronal and a glial cell tauopathy can accompany the TDP-43 proteinopathy in patients with motor neurone disease (MND) with cognitive changes, and that the tauopathy may be fundamental to disease pathogenesis and clinical phenotype. In the present study, we sought to substantiate these latter findings, and test this concept of a pathological continuum, in a consecutive series of 41 patients with MND, 16 with FTD + MND and 23 with FTD without MND.

View Article and Find Full Text PDF

Introduction: Many neurodegenerative diseases are characterised by accumulations of misfolded proteins that can colocalise with chaperone proteins (for example, heat shock protein 27 (HSP27)), which might act as modulators of protein aggregation.

Methods: The role of HSP27 in the pathogenesis of neurodegenerative disorders such as frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD) and motor neuron disease (MND) was investigated. We used immunohistochemical and Western blot analysis to determine the distribution and amount of this protein in the frontal and temporal cortices of diseased and control subjects.

View Article and Find Full Text PDF

We have measured plasma progranulin and interleukin-6 in 230 patients with frontotemporal lobar degeneration (FTLD), 104 patients with Alzheimer's disease, and 161 control subjects. We have replicated previous findings of decreased levels of progranulin protein in FTLD because of mutations in GRN and show this is not observed in FTLD cases because of other causes. interleukin-6 levels were increased in FTLD overall, but these did not discriminate between clinical and genetic subtypes.

View Article and Find Full Text PDF

Aims: Frontotemporal lobar degeneration (FTLD) and motor neurone disease are linked by the possession of a hexanucleotide repeat expansion in C9ORF72, and both show neuronal cytoplasmic inclusions within cerebellar and hippocampal neurones which are TDP-43 negative but immunoreactive for p62 and dipeptide repeat proteins (DPR), these being generated by a non-ATG RAN translation of the expanded region of the gene.

Methods: Twenty-two cases of FTLD from Newcastle were analysed for an expansion in C9ORF72 by repeat primed PCR and Southern blot. Detailed case note analysis was performed, and blinded retrospective clinical impressions were achieved by review of clinical histories.

View Article and Find Full Text PDF

A hexanucleotide (GGGGCC) expansion in C9ORF72 gene is the most common genetic change seen in familial Frontotemporal Lobar Degeneration (FTLD) and familial Motor Neurone Disease (MND). Pathologically, expansion bearers show characteristic p62 positive, TDP-43 negative inclusion bodies within cerebellar and hippocampal neurons which also contain dipeptide repeat proteins (DPR) formed from sense and antisense RAN (repeat associated non ATG-initiated) translation of the expanded repeat region itself. 'Inappropriate' formation, and aggregation, of DPR might therefore confer neurotoxicity and influence clinical phenotype.

View Article and Find Full Text PDF

Synopsis of recent research by authors named "Yvonne S Davidson"

  • - Yvonne S Davidson's recent research focuses on neurodegenerative disorders, particularly Alzheimer's disease and associated pathologies, investigating factors such as cognitive impairment, genetic influences, and the relationship between vascular and neurodegenerative changes.
  • - Notable findings include the association between self-reported late-life hypertension and improved cognitive status, alongside insights into the pathological mechanisms underlying conditions like corticobasal syndrome and TDP-43 proteinopathies.
  • - Davidson's work emphasizes the importance of early detection and intervention strategies for Alzheimer's disease by identifying cognitive markers and exploring the neurobiological correlates of cognitive decline in various disease contexts.