Browsing by Subject "Blood-based biomarkers"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Blood-based tumor biomarkers in lung cancer for detection and treatment
    (2017-11) Mamdani, Hirva; Ahmed, Shahid; Armstrong, Samantha; Mok, Tony; Jalal, Shadia I.; Medicine, School of Medicine
    The therapeutic landscape of lung cancer has expanded significantly over the past decade. Advancements in molecularly targeted therapies, strategies to discover and treat resistance mutations, and development of personalized cancer treatments in the context of tumor heterogeneity and dynamic tumor biology have made it imperative to obtain tumor samples on several different occasions through the course of patient treatment. While this approach is critical to the delivery of optimal cancer treatment, it is fraught with a number of barriers including the need for invasive procedures with associated complications, access to limited amount of tissue, logistical delays in obtaining the biopsy, high healthcare cost, and in many cases inability to obtain tissue because of technically difficult location of the tumor. Given multiple limitations of obtaining tissue samples, the use of blood-based biomarkers (“liquid biopsies”) may enable earlier diagnosis of cancer, lower costs by avoiding complex invasive procedures, tailoring molecular targeted treatments, improving patient convenience, and ultimately supplement clinical oncologic decision-making. In this paper, we review various blood-based biomarkers including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), tumor derived exosomes, tumor educated platelets (TEPs), and microRNA; and highlight current evidence for their use in detection and treatment of lung cancer.
  • Thumbnail Image
    Item
    Effects of Vascular Risk Factors on the Association of Blood-Based Biomarkers with Alzheimer's Disease
    (European Society of Medicine, 2023) Hoost, S. S.; Brickman, A. M.; Manly, J. J.; Honig, L. S.; Gu, Y.; Sanchez, D.; Reyes-Dumeyer, D.; Lantigua, R. A.; Kang, M. S.; Dage, J. L.; Mayeux, R.; Neurology, School of Medicine
    Background: Comorbidities may influence the levels of blood-based biomarkers for Alzheimer's disease (AD). We investigated whether differences in risk factors or comorbid conditions might explain the discordance between clinical diagnosis and biomarker classifications in a multi-ethnic cohort of elderly individuals. Aims: To evaluate the relationship of medical conditions and other characteristics, including body mass index (BMI), vascular risk factors, and head injury, with cognitive impairment and blood-based biomarkers of AD, phosphorylated tau (P-tau 181, P-tau 217), in a multi-ethnic cohort. Methods: Three-hundred individuals, aged 65 and older, were selected from a prospective community-based cohort for equal representation among three racial/ethnic groups: non-Hispanic White, Hispanic/Latino and African American/Black. Participants were classified into four groups based on absence (Asym) or presence (Sym) of cognitive impairment and low (NEG) or high (POS) P-tau 217 or P-tau 181 levels, determined previously in the same cohort: (Asym/NEG, Asym/POS, Sym/NEG, Sym/POS). We examined differences in individual characteristics across the four groups. We performed post-hoc analysis examining the differences across biomarker and cognitive status. Results: P-tau 217 or P-tau 181 positive individuals had lower BMI than P-tau negative participants, regardless of symptom status. Symptomatic and asymptomatic participants did not differ in terms of BMI. BMI was not a mediator of the effect of P-tau 217 or P-tau 181 on dementia. Frequencies of other risk factors did not differ between the four groups of individuals. Conclusions: Participants with higher levels of P-tau 217 or P-tau 181 consistent with AD had lower BMI regardless of whether the individual was symptomatic. These findings suggest that weight loss may change with AD biomarker levels before onset of cognitive decline. They do not support BMI as a confounding variable. Further longitudinal studies could explore the relationship of risk factors with clinical diagnoses and biomarkers.
  • Thumbnail Image
    Item
    Feasibility and Acceptability of Using Plasma Biomarkers for Diagnosing Alzheimer’s Disease in Primary Care
    (Oxford University Press, 2023-12-21) Fowler, Nicole; Swartzell, Kristen; Hammers, Dustin; Brosch, Jared; Murray, James; Willis, Deanna; Medicine, School of Medicine
    Blood-based biomarkers (Aβ, P-tau, neurofilament light) are clinically available to aid in the diagnosis of Alzheimer’s disease and related dementias (ADRD). However, no research has examined the use of blood biomarkers to aid in the diagnosis of ADRD in primary care (PC). Our study will test feasibility and acceptability of implementing blood-based biomarkers for ADRD in PC. Participants include: all PC patients ≥65 years presenting to one of six PC clinics between 6/1/22 and 5/31/23 who score cognitively impaired on the Linus Health Digital Clock and Recall (DCR™), and PC providers (PCPs) of these patients. Patients will view a decision guide about biomarkers and complete the Concerns about Alzheimer’s Disease Dementia Scale, and the Future Time Perspective Scale and the Impact of Events Scale. These measures and the PHQ-9 and GAD-7 will be repeated within 2 weeks of results disclosure. PCPs will receive training on biomarker disclosure techniques and best practices. To date 9 PCPs have consented to provide the biomarker results disclosure and 11 have declined. Following completion of PCP consent (n=100), a total of 200 patients who failed the DCR are eligible to be approached for consent. By November 2023, we anticipate that 150 patients will have completed biomarker testing, and we will have examined the biomarker results in the context of patient neuropsychological and clinical data, comorbidities, and sociodemographic information. This study will provide information regarding feasibility and utility of ADRD biomarkers in PC and a preliminary analysis of biomarker results compared with the patients’ clinical profiles.
  • Thumbnail Image
    Item
    Plasma p‐tau181, p‐tau217, and other blood‐based Alzheimer's disease biomarkers in a multi‐ethnic, community study
    (Wiley, 2021) Brickman, Adam M.; Manly, Jennifer J.; Honig, Lawrence S.; Sanchez, Danurys; Reyes-Dumeyer, Dolly; Lantigua, Rafael A.; Lao, Patrick J.; Stern, Yaakov; Vonsattel, Jean Paul; Teich, Andrew F.; Airey, David C.; Proctor, Nicholas Kyle; Dage, Jeffrey L.; Mayeux, Richard; Neurology, School of Medicine
    Introduction: Blood-based Alzheimer's disease (AD) biomarkers provide opportunities for community studies and across ethnic groups. We investigated blood biomarker concentrations in the Washington Heights-Inwood Columbia Aging Project (WHICAP), a multi-ethnic community study of aging and dementia. Methods: We measured plasma amyloid beta (Aβ)40, Aβ42, total tau (t-tau), phosphorylated tau (p-tau)181, and p-tau217, and neurofilament light chain (NfL) in 113 autopsied participants (29% with high AD neuropathological changes) and in 300 clinically evaluated individuals (42% with clinical AD). Receiver operating characteristics were used to evaluate each biomarker. We also investigated biomarkers as predictors of incident clinical AD. Results: P-tau181, p-tau217, and NfL concentrations were elevated in pathologically and clinically diagnosed AD. Decreased Aβ42/Aβ40 ratio and increased p-tau217 and p-tau181 were associated with subsequent AD diagnosis. Discussion: Blood-based AD biomarker concentrations are associated with pathological and clinical diagnoses and can predict future development of clinical AD, providing evidence that they can be incorporated into multi-ethnic, community-based studies.
  • Thumbnail Image
    Item
    Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease
    (Elsevier, 2020-08-01) Schultz, Stephanie A.; Strain, Jeremy F.; Adedokun, Adedamola; Wang, Qing; Preische, Oliver; Kuhle, Jens; Flores, Shaney; Keefe, Sarah; Dincer, Aylin; Ances, Beau M.; Berman, Sarah B.; Brickman, Adam M.; Cash, David M.; Chhatwal, Jasmeer; Cruchaga, Carlos; Ewers, Michael; Fox, Nick N.; Ghetti, Bernardino; Goate, Alison; Graff-Radford, Neill R.; Hassenstab, Jason J.; Hornbeck, Russ; Jack, Clifford; Johnson, Keith; Joseph-Mathurin, Nelly; Karch, Celeste M.; Koeppe, Robert A.; Lee, Athene K. W.; Levin, Johannes; Masters, Colin; McDade, Eric; Perrin, Richard J.; Rowe, Christopher C.; Salloway, Stephen; Saykin, Andrew J.; Sperling, Reisa; Su, Yi; Villemagne, Victor L.; Vöglein, Jonathan; Weiner, Michael; Xiong, Chengjie; Fagan, Anne M.; Morris, John C.; Bateman, Randall J.; Benzinger, Tammie L. S.; Jucker, Mathias; Gordon, Brian A.; Pathology and Laboratory Medicine, School of Medicine
    Neurofilament light chain (NfL) is a protein that is selectively expressed in neurons. Increased levels of NfL measured in either cerebrospinal fluid or blood is thought to be a biomarker of neuronal damage in neurodegenerative diseases. However, there have been limited investigations relating NfL to the concurrent measures of white matter (WM) decline that it should reflect. White matter damage is a common feature of Alzheimer's disease. We hypothesized that serum levels of NfL would associate with WM lesion volume and diffusion tensor imaging (DTI) metrics cross-sectionally in 117 autosomal dominant mutation carriers (MC) compared to 84 non-carrier (NC) familial controls as well as in a subset (N = 41) of MC with longitudinal NfL and MRI data. In MC, elevated cross-sectional NfL was positively associated with WM hyperintensity lesion volume, mean diffusivity, radial diffusivity, and axial diffusivity and negatively with fractional anisotropy. Greater change in NfL levels in MC was associated with larger changes in fractional anisotropy, mean diffusivity, and radial diffusivity, all indicative of reduced WM integrity. There were no relationships with NfL in NC. Our results demonstrate that blood-based NfL levels reflect WM integrity and supports the view that blood levels of NfL are predictive of WM damage in the brain. This is a critical result in improving the interpretability of NfL as a marker of brain integrity, and for validating this emerging biomarker for future use in clinical and research settings across multiple neurodegenerative diseases.