Publications by authors named "Wilcock D"

Anti-Aβ immunotherapy use to treat Alzheimer's disease is on the rise. While anti-Aβ antibodies provide hope in targeting Aβ plaques in the brain there still remains a lack of understanding regarding the cellular responses to these antibodies in the brain. In this study we sought to identify acute effects of anti-Aβ antibody on immune responses.

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The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell-mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias (ADRD) remain unclear. Furthermore, the roles of the peripheral immune system in driving ADRD pathology remain incompletely elucidated.

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Introduction: Placental growth factor (PlGF) may regulate cerebrovascular permeability. We hypothesized that white matter interstitial fluid accumulation, estimated via magnetic resonance imaging (MRI) free water (FW), would explain the associations between elevated PlGF, white matter hyperintensities (WMH), and cognitive impairment.

Methods: MarkVCID consortium participants ≥55 years old with plasma PlGF and brain MRI were included.

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Article Synopsis
  • 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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  • 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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  • Common neuropathologies linked to dementia include Alzheimer's disease neuropathologic change (ADNC) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), with biofluid proteomics playing a key role in understanding their biology.
  • A study at the University of Kentucky assessed cerebrospinal fluid (CSF) from 29 older adults, categorizing them into LATE-NC+ (9 cases with advanced LATE-NC) and LATE-NC- (20 cases without it).
  • Out of nearly 950 proteins identified, only 4 showed significant differences between the two groups, with RBP4 being notably higher in LATE-NC+ cases, suggesting a
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Background And Purpose: The immune response changes during aging and the progression of Alzheimer's disease (AD) and related dementia (ADRD). Terminally differentiated effector memory T cells (called T) are important during aging and AD due to their cytotoxic phenotype and association with cognitive decline. However, it is not clear if the changes seen in T are specific to AD-related cognitive decline specifically or are more generally correlated with cognitive decline.

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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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Adults with Down syndrome are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease and is linked to a diagnosis of dementia in adults with Down syndrome via structural imaging markers of cerebrovascular disease and atrophy.

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The targeting of amyloid-beta (Aβ) plaques therapeutically as one of the primary causes of Alzheimer's disease (AD) dementia has been an ongoing effort spanning decades. While some antibodies are extremely promising and have been moved out of clinical trials and into the clinic, most of these treatments show similar adverse effects in the form of cerebrovascular damage known as amyloid-related imaging abnormalities (ARIA). The two categories of ARIA are of major concern for patients, families, and prescribing physicians, with ARIA-E presenting as cerebral edema, and ARIA-H as cerebral hemorrhages (micro- and macro-).

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EGFR amplification in gliomas is commonly defined by an EGFR/CEP7 ratio of ≥2. In testing performed at a major reference laboratory, a small subset of patients had ≥5 copies of both EGFR and CEP7 yet were not amplified by the EGFR/CEP7 ratio and were designated high polysomy cases. To determine whether these tumors are more closely related to traditionally defined EGFR-amplified or nonamplified gliomas, a retrospective search identified 22 out of 1143 (1.

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Vascular contributions to cognitive impairment and dementia (VCID) is an all-encompassing term that describes cognitive impairment due to cerebrovascular origins. With the advancement of imaging and pathological studies, we now understand that VCID is often comorbid with Alzheimer disease. While researchers in the Alzheimer disease field have been working for years to establish and test blood-based biomarkers for Alzheimer disease diagnosis, prognosis, clinical therapy discovery, and early detection, blood-based biomarkers for VCID are in their infancy and also face challenges.

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Background: Novel and comprehensive approaches are needed to address shortcomings in the diversity and inclusiveness of the scientific workforce. In response to this need and informed by multiple programs and data sources, we created the Research Scholars Program (RSP). The RSP is a yearlong program for early-career faculty with an overall objective to overcome barriers to the academic success, retention, progression, and promotion of groups underrepresented in biomedical and behavioral research.

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Background And Purpose: The immune response changes during aging and the progression of Alzheimer's disease (AD) and related dementia (ADRD). Terminally differentiated effector memory T cells (called TEMRA) are important during aging and AD due to their cytotoxic phenotype and association with cognitive decline. However, it is not clear if the changes seen in T are specific to AD-related cognitive decline specifically or are more generally correlated with cognitive decline.

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Importance: By age 40 years over 90% of adults with Down syndrome (DS) have Alzheimer's disease (AD) pathology and most progress to dementia. Despite having few systemic vascular risk factors, individuals with DS have elevated cerebrovascular disease (CVD) markers that track with the clinical progression of AD, suggesting a role for CVD that is hypothesized to be mediated by inflammatory factors.

Objective: To examine the pathways through which small vessel CVD contributes to AD-related pathophysiology and neurodegeneration in adults with DS.

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Introduction: Protein-based plasma assays provide hope for improving accessibility and specificity of molecular diagnostics to diagnose dementia.

Methods: Plasma was obtained from participants (N = 837) in our community-based University of Kentucky Alzheimer's Disease Research Center cohort. We evaluated six Alzheimer's disease (AD)- and neurodegeneration-related (Aβ40, Aβ42, Aβ42/40, p-tau181, total tau, and NfLight) and five inflammatory biomarkers (TNF𝛼, IL6, IL8, IL10, and GFAP) using the SIMOA-based protein assay platform.

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Research on the cerebrovasculature may provide insights into brain health and disease. Immunohistochemical staining is one way to visualize blood vessels, and digital pathology has the potential to revolutionize the measurement of blood vessel parameters. These tools provide opportunities for translational mouse model research.

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Individuals with Down syndrome (DS) are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease, entorhinal cortical atrophy, and diagnosis of dementia in adults with DS.

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Context.—: The American Society of Clinical Oncology/College of American Pathologists 2018 update of the human epidermal growth factor receptor 2 (HER2) testing guideline includes a fluorescence in situ hybridization (FISH) group with a HER2 to chromosome 17 centromere (CEP17) ratio less than 2.0 and HER2 copy number 6.

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Article Synopsis
  • People with dementia experience increased brain inflammation linked to immune cells, but the effects on the systemic immune system are unclear.
  • A study analyzed immune cells from older adults to determine if early cognitive impairment is associated with specific inflammatory cytokine patterns.
  • Results showed that women with cognitive impairment had lower T17 cytokine levels after T-cell stimulation, indicating a potential early systemic change that may affect immunity in older adults.
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Background: White matter hyperintensities (WMH) that occur in the setting of vascular cognitive impairment and dementia (VCID) may be dynamic increasing or decreasing volumes or stable over time. Quantifying such changes may prove useful as a biomarker for clinical trials designed to address vascular cognitive-impairment and dementia and Alzheimer's Disease.

Objective: Conducting multi-site cross-site inter-rater and test-retest reliability of the MarkVCID white matter hyperintensity growth and regression protocol.

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Aims: We sought to identify and optimise a universally available histological marker for pericytes in the human brain. Such a marker could be a useful tool for researchers. Further, identifying a gene expressed relatively specifically in human pericytes could provide new insights into the biological functions of this fascinating cell type.

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