Publications by authors named "Elizabeth Head"

Introduction: Adults with Down syndrome demonstrate striatum-first amyloid accumulation with [ C]PiB PET imaging, which has not been replicated with [ F]florbetapir (FBP). Early striatal accumulation has not been temporally quantified with respect to global cortical measures.

Methods: Longitudinal PiB (n=175 participants) and FBP (n=92 participants) data from the Alzheimer Biomarkers Consortium-Down Syndrome were used to measure cortical and striatal binding.

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Introduction: This study investigated the impact of trisomy 21 mosaicism (mT21) on Alzheimer's disease (AD) neuropathology in a well-characterized clinical case described by Ringman et al.

Methods: We describe AD neuropathology in mT21 including amyloid beta, phosphorylated tau, astrogliosis, microgliosis, α-synuclein, and TAR DNA-binding protein 43 (TDP-43) in cerebral cortex, hippocampal subregions, and amygdala using immunohistochemistry.

Results: We observed high AD neuropathologic change with a score of A3B3C3.

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The locus coeruleus (LC) is among the first brain structures impacted by Alzheimer's disease (AD), and noradrenergic denervation may contribute to early neurovascular dysfunction in AD. Mechanistic links between the LC and cerebral perfusion have been demonstrated in rodents, but there have been no similar studies in aging humans. Community-dwelling older adults with no history of stroke or dementia (N=66) underwent structural (T1-MPRAGE; T1-FSE) and perfusion (resting pCASL) MRI.

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  • - The study investigates the complex causes of Alzheimer's disease (AD) by using advanced techniques to analyze genetic information from both sporadic AD and Down Syndrome-related AD (DSAD). - Researchers found specific changes in gene expression linked to where pathology accumulates in the brain's cortical layers, highlighting inflammation in upper layers as significant in AD. - The study also compared findings from human samples to data from an amyloid model in mice to better understand how amyloid-related changes affect gene expression across different species.
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  • This study focused on the risk of Alzheimer's disease in adults with Down syndrome, using amyloid and tau PET imaging to track disease progression.
  • It involved a longitudinal analysis of 167 participants, assessing cognitive functioning and biomarkers over two visits between 2017 and 2022.
  • The research aimed to determine the timeline for symptomatic Alzheimer's based on "amyloid age" and its relation to cognitive decline and tau accumulation.
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Introduction: Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment.

Methods: One hundred sixty-one older adults free of dementia or major neurological/psychiatric disorders were recruited.

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Brain signaling of calcineurin (CN) and nuclear factor of activated T-cells (NFAT) transcription factor increases in Alzheimer disease (AD) and is associated with synaptic loss, neurodegeneration, neuroinflammation, amyloid-β (Aβ) production, and cognitive decline. CN/NFAT inhibitors ameliorate these neuropathologies in mouse models of AD. Further, chronic use of tacrolimus in transplant patients reduces risk of AD.

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  • Blood-based biomarkers are being studied to improve the detection and monitoring of Alzheimer's Disease in individuals with Down Syndrome, as current clinical diagnostics are challenging.
  • Key biomarkers like phosphorylated tau (p-tau217, p-tau181) have shown strong connections to disease progression in Down Syndrome, suggesting they could be valuable in clinical settings.
  • The research emphasizes the need for more understanding of biomarker variability, particularly regarding sex differences and the appropriate contexts for their clinical application in Alzheimer's diagnosis and treatment.
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  • - Development of Alzheimer's disease (AD) pathology occurs faster in individuals with Down's syndrome (DS) compared to others; this study focuses on comparing specific biomarkers in DS individuals and their siblings.
  • - Researchers found that plasma levels of glial fibrillary acidic protein (GFAP) and pTau-217 were elevated in individuals with DS, indicating increased astrogliosis and tau pathology, and GFAP played a mediating role in the relationship between amyloid and tau levels.
  • - The findings suggest that astrogliosis is crucial in the early stages of Alzheimer's in DS, and targeting neuroinflammation might be beneficial primarily for those with amyloid positivity.
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  • - Individuals with Down syndrome (DS) face a high risk of developing Alzheimer's disease (AD), but about 20% do not show dementia symptoms until later in life, potentially due to the presence of mosaicism, which can reduce gene expression from chromosome 21.
  • - Researchers analyzed data from two major studies (ABC-DS and a legacy study) that included neuropsychological assessments and biomarkers to determine the prevalence and impact of mosaicism, finding it in less than 10% of participants.
  • - Those with mosaicism exhibited lower levels of AD-related biomarkers and a slower decline in cognitive scores compared to individuals with full trisomy, indicating a potential protective effect against dementia, though more research is needed to fully understand these findings.
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  • By age 40, over 90% of adults with Down syndrome develop Alzheimer’s disease, with many progressing to dementia, despite having few typical vascular risk factors.
  • This study analyzed how small vessel cerebrovascular disease impacts Alzheimer's disease progression and neurodegeneration in adults with Down syndrome, using MRI and plasma biomarker data from 185 participants.
  • Results indicated a complex relationship where white matter hyperintensity (WMH) levels influenced phosphorylated tau, linked by glial fibrillary acidic protein, suggesting that cerebrovascular health affects Alzheimer’s pathology in this population.
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  • Aging leads to the buildup of proteins that behave like amyloid, but how these proteins form isn't fully understood.
  • Researchers found that errors in messenger RNA cause amyloid-like proteins to be produced in various human cell types, including stem cells and neurons.
  • These errors increase with DNA damage, which is commonly associated with aging, suggesting a connection between normal aging processes and age-related diseases.
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Introduction: Limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathologic change (LATE-NC) staging criteria were updated in 2023. We evaluated this updated staging using National Alzheimer's Coordinating Center data.

Methods: We examined associations of LATE-NC stages with cognition and other neuropathologic changes (NCs), and with cognition while accounting for other NCs, using multilevel regression models.

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  • The study focuses on neurodegenerative diseases, specifically tauopathies like Pick's disease and Alzheimer's, investigating their regulatory mechanisms through epigenomic variations.
  • Researchers identified key regulatory changes associated with disease progression, revealing potential new therapeutic targets and linking specific non-coding regions and transcription factor binding to target genes.
  • They validated findings using CRISPR techniques and created an interactive database to visualize transcription factor occupancy and regulatory networks in single cells.
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  • Down syndrome (DS) individuals commonly develop Alzheimer's disease (AD) by age 50, and this study investigates the early AD pathology in the locus coeruleus (LC) pertaining to both DS-AD and sporadic AD.* -
  • The research involved analyzing postmortem human tissue samples from 36 cases (including controls, DS-AD, and AD) to identify differences in the levels of tau and amyloid-β, revealing significantly higher levels of oligomeric tau and Aβ in DS-AD compared to other AD cases.* -
  • The findings suggest that DS-AD shows unique pathological features, similar to early-onset AD, which could help inform future research on the mechanisms driving AD progression in
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  • The study investigates the relationship between amyloid-beta (Aβ) and tau biomarkers and the onset of symptomatic Alzheimer's disease (AD) in adults with Down syndrome (DS), highlighting the concept of "amyloid age."* -
  • It analyzes data from 167 adults with DS over roughly five years, finding that cognitive decline becomes noticeable about 2.7 years after reaching Aβ+ status, with tau levels also increasing subsequently.* -
  • The findings suggest a quicker progression to cognitive impairment and dementia in individuals with DS compared to typical late-onset AD, emphasizing the relevance of amyloid age for clinical practice and research.*
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  • Anti-β-amyloid immunotherapy with lecanemab shows promise for Alzheimer’s patients, particularly those with Down syndrome, who develop Alzheimer-like brain changes by their 40s.
  • A study analyzed postmortem brain tissue from 15 individuals with Down syndrome to assess how well lecanemab binds to amyloid plaques and blood vessels in the brain.
  • Results indicated that while lecanemab effectively binds to amyloid plaques, it also binds significantly to blood vessels, raising safety concerns and highlighting the need for careful clinical trials in this population.
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Visit-to-visit blood pressure variability (BPV) predicts age-related hippocampal atrophy, neurodegeneration, and memory decline in older adults. Beat-to-beat BPV may represent a more reliable and efficient tool for prospective risk assessment, but it is unknown whether beat-to-beat BPV is similarly associated with hippocampal neurodegeneration, or with plasma markers of neuroaxonal/neuroglial injury. Independently living older adults without a history of dementia, stroke, or other major neurological disorders were recruited from the community (N = 104; age = 69.

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Background: Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment.

Methods: 161 older adults free of dementia or major neurological/psychiatric disorders were recruited.

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TDP-43 proteinopathy is a salient neuropathologic feature in a subset of frontotemporal lobar degeneration (FTLD-TDP), in amyotrophic lateral sclerosis (ALS-TDP), and in limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and is associated with hippocampal sclerosis of aging (HS-A). We examined TDP-43-related pathology data in the National Alzheimer's Coordinating Center (NACC) in two parts: (I) availability of assessments, and (II) associations with clinical diagnoses and other neuropathologies in those with all TDP-43 measures available. Part I: Of 4326 participants with neuropathology data collected using forms that included TDP-43 assessments, data availability was highest for HS-A (97%) and ALS (94%), followed by FTLD-TDP (83%).

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  • * Key findings include her ApoE genotype (E2/3) linked to a lower dementia risk, neuroimaging showing stable amyloid and moderate tau levels, and intermediate Alzheimer’s pathology with added Lewy body and cerebrovascular issues.
  • * The study highlights the complex relationship between Alzheimer's symptoms and brain changes in Down syndrome, suggesting the need for more research on factors that contribute to cognitive resilience in this population.
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Background: Higher order regulation of autonomic function is maintained by the coordinated activity of specific cortical and subcortical brain regions, collectively referred to as the central autonomic network (CAN). Autonomic changes are frequently observed in Alzheimer's disease (AD) and dementia, but no studies to date have investigated whether plasma AD biomarkers are associated with CAN functional connectivity changes in at risk older adults.

Methods: Independently living older adults (N = 122) without major neurological or psychiatric disorder were recruited from the community.

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Adults with Down syndrome have a genetic form of Alzheimer's disease (AD) and evidence of cerebrovascular disease across the AD continuum, despite few systemic vascular risk factors. The onset and progression of AD in Down syndrome is highly age-dependent, but it is unknown at what age cerebrovascular disease emerges and what factors influence its severity. In the Alzheimer's Biomarker Consortium-Down Syndrome study (ABC-DS; n = 242; age = 25-72), we estimated the age inflection point at which MRI-based white matter hyperintensities (WMH), enlarged perivascular spaces (PVS), microbleeds, and infarcts emerge in relation to demographic data, risk factors, amyloid and tau, and AD diagnosis.

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The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24).

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Numerous research groups worldwide have focused on postmortem imaging to bridge the resolution gap between clinical neuroimaging and neuropathology data. We developed a standardized protocol for brain embedding, imaging, and processing, facilitating alignment between antemortem MRI, postmortem MRI, and pathology to observe brain atrophy and structural damage progression over time. Using 7T postmortem ex vivo MRI, we explore the potential correlation of amygdala and hippocampal atrophy with neuropathological burden in both Down syndrome (DS) and Alzheimer's disease (AD) cohorts.

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