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Biomarkers.
Alzheimers Dement
December 2024
University of Southern California, Los Angeles, CA, USA.
Background: The apolipoprotein E (ApoE) Ɛ4 allele is associated with a significant risk for both late-onset Alzheimer's Disease (AD) development and cerebral amyloidosis, but the degree to which cerebrospinal fluid (CSF) apoE glycosylation affects disease progression is unclear. The objective of this study was to examine the relationship of CSF apoE glycosylation with t-tau, p-tau181, and Aβ1-42 CSF levels, and to delineate the effect of the APOE4+ genotype (vs E4-) on glycosylation.
Method: Total glycosylation and apoE isoform-specific glycosylation were analyzed in baseline plasma and CSF samples from a longitudinal cohort of older individuals (n=188, ages 55 - 89) from the Alzheimer's Disease Neuroimaging Initiative (ADNI).
Developing Topics.
Alzheimers Dement
December 2024
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Background: Increased white matter hyperintensity volume (WMH) visible on MRI is a common finding in Alzheimer's disease (AD) and is often attributed to small vessel ischemic changes. We hypothesized that WMH in preclinical AD is associated with worsening of vessel amyloidosis manifested as microhemorrhages (mH, ARIA-H). We examine this hypothesis using cross-sectional and longitudinal data over 4.
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Alzheimers Dement
December 2024
University of Kentucky College of Medicine, Sanders-Brown Center on Aging, Lexington, KY, USA.
Background: Vascular pathology profoundly comorbid with AD pathology could worsen disease progression and reduce treatment efficacy. Knowledge of small vessels and cerebrovascular function in AD mouse models is limited. Investigating vascular related aspects for preclinical AD studies is essential for biomarker development and treatment trials.
View Article and Find Full Text PDFBackground: Evidence for abnormal amyloid-β (Aβ) plaque accumulation is necessary prior to initiating anti-amyloid therapy in early symptomatic Alzheimer's disease (AD). While the clinical trials for lecanemab and related drugs utilized positron emission tomography (PET) to demonstrate brain amyloidosis, current appropriate use recommendations for clinical practice consider PET or cerebrospinal fluid (CSF) biomarkers as satisfactory for this purpose. Here, we present four clinical cases where CSF biomarker results were discordant from amyloid PET, with the potential to result in erroneous treatment targeting.
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Alzheimers Dement
December 2024
University of Kentucky College of Medicine, Sanders-Brown Center on Aging, Lexington, KY, USA.
Background: Vascular contributions to cognitive impairment and dementia (VCID) results from cerebrovascular injuries, significantly contributing to age-related cognitive decline, and coexists with Alzheimer's disease (AD) in excess of 70% of AD patients. These co-occurring neuropathological subtypes are referred to as mixed-etiology dementia (MED). Despite the prevalence of MED little is known regarding the neuroinflammatory responses of microglia in the context of vascular injury in tissues already containing AD-related cerebral amyloidosis.
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