Rawan Tarawneh

University of Washington Seattle, Seattle, WA, United States

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Publications (10)43.25 Total impact

  • Alzheimer disease and associated disorders 08/2013; · 2.88 Impact Factor
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    Rawan Tarawneh, David M Holtzman
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    ABSTRACT: Alzheimer disease (AD) is the most common cause of dementia in the elderly. Clinicopathological studies support the presence of a long preclinical phase of the disease, with the initial deposition of AD pathology estimated to begin approximately 10-15 years prior to the onset of clinical symptoms. The hallmark clinical phenotype of AD is a gradual and progressive decline in two or more cognitive domains, most commonly involving episodic memory and executive functions, that is sufficient to cause social or occupational impairment. Current diagnostic criteria can accurately identify AD in the majority of cases. As disease-modifying therapies are being developed, there is growing interest in the identification of individuals in the earliest symptomatic, as well as presymptomatic, stages of disease, because it is in this population that such therapies may have the greatest chance of success. The use of informant-based methods to establish cognitive and functional decline of an individual from previously attained levels of performance best allows for the identification of individuals in the very mildest stages of cognitive impairment.
    Cold Spring Harbor perspectives in medicine. 05/2012; 2(5):a006148.
  • Clinical Chemistry 04/2012; · 7.15 Impact Factor
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    ABSTRACT: Measures of neuronal damage/dysfunction are likely good surrogates for disease progression in Alzheimer disease (AD). CSF markers of neuronal injury may offer utility in predicting disease progression and guiding prognostic and outcome assessments in therapeutic trials. Visinin-like protein-1 (VILIP-1) has demonstrated potential utility as a marker of neuronal injury. We here investigate the utility of VILIP-1 and VILIP-1/Aβ42 in predicting rates of cognitive decline in early AD. Individuals with a clinical diagnosis of very mild or mild AD (n = 60) and baseline CSF measures of VILIP-1, tau, p-tau181, and Aβ42 were followed longitudinally for an average of 2.6 years. Annual assessments included the Clinical Dementia Rating (CDR), CDR-sum of boxes (CDR-SB), and global composite scores. Mixed linear models assessed the ability of CSF biomarker measures to predict rates of cognitive decline over time. Baseline CSF VILIP-1 and VILIP-1/Aβ42 levels predicted rates of future decline in CDR-SB and global composite scores over the follow-up period. Individuals with CSF VILIP-1 ≥560 pg/mL (corresponding to the upper tercile) progressed much more rapidly in CDR-SB (1.61 boxes/year; p = 0.0077) and global scores (-0.53 points/year; p = 0.0002) than individuals with lower values (0.85 boxes/year and -0.15 points/year, respectively) over the follow-up period. CSF tau, p-tau181, tau/Aβ42, and p-tau181/Aβ42 also predicted more rapid cognitive decline in CDR-SB and global scores over time. These findings suggest that CSF VILIP-1 and VILIP-1/Aβ42 predict rates of global cognitive decline similarly to tau and tau/Aβ42, and may be useful CSF surrogates for neurodegeneration in early AD.
    Neurology 03/2012; 78(10):709-19. · 8.25 Impact Factor
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    ABSTRACT: There is a growing need to identify cerebrospinal fluid (CSF) markers that can detect Alzheimer's disease (AD) pathology in cognitively normal individuals because it is in this population that disease-modifying therapies may have the greatest chance of success. While AD pathology is estimated to begin ~10-15 years prior to the onset of cognitive decline, substantial neuronal loss is present by the time the earliest signs of cognitive impairment appear. Visinin-like protein-1 (VILIP-1) has demonstrated potential utility as a marker of neuronal injury. Here we investigate CSF VILIP-1 and VILIP-1/amyloid-β42 (Aβ42) ratio as diagnostic and prognostic markers in early AD. We assessed CSF levels of VILIP-1, tau, phosphorylated-tau181 (p-tau181), and Aβ42 in cognitively normal controls (CNC) (n = 211), individuals with early symptomatic AD (n = 98), and individuals with other dementias (n = 19). Structural magnetic resonance imaging (n = 192) and amyloid imaging with Pittsburgh Compound-B (n = 156) were obtained in subsets of this cohort. Among the CNC cohort, 164 individuals had follow-up annual cognitive assessments for 2-3 years. CSF VILIP-1 levels differentiated individuals with AD from CNC and individuals with other dementias. CSF VILIP-1 levels correlated with CSF tau, p-tau181, and brain volumes in AD. VILIP-1 and VILIP-1/Aβ42 predicted future cognitive impairment in CNC over the follow-up period. Importantly, CSF VILIP-1/Aβ42 predicted future cognitive impairment at least as well as tau/Aβ42 and p-tau181/Aβ42. These findings suggest that CSF VILIP-1 and VILIP-1/Aβ42 offer diagnostic utility for early AD, and can predict future cognitive impairment in cognitively normal individuals similarly to tau and tau/Aβ42, respectively.
    Annals of Neurology 08/2011; 70(2):274-85. · 11.19 Impact Factor
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    Rawan Tarawneh, James E Galvin
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    ABSTRACT: The cellular mechanisms underlying neuronal loss and neurodegeneration have been an area of interest in the last decade. Although neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and Huntington disease each have distinct clinical symptoms and pathologies, they all share common mechanisms such as protein aggregation, oxidative injury, inflammation, apoptosis, and mitochondrial injury that contribute to neuronal loss. Although cerebrovascular disease has different causes from the neurodegenerative disorders, many of the same common disease mechanisms come into play following a stroke. Novel therapies that target each of these mechanisms may be effective in decreasing the risk of disease, abating symptoms, or slowing down their progression. Although most of these therapies are experimental, and require further investigation, a few seem to offer promise.
    Clinics in Geriatric Medicine 02/2010; 26(1):125-47. · 3.14 Impact Factor
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    Rawan Tarawneh, David M Holtzman
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    ABSTRACT: The identification and characterization of amyloid-beta (Abeta) and tau as the main pathological substrates of Alzheimer's disease (AD) have driven many efforts in search for suitable biomarkers for AD. In the last decade, research in this area has focused on developing a better understanding of the principles that govern protein deposition, mechanisms that link aggregation to toxicity and neuronal death, and a better understanding of protein dynamics in brain tissue, interstitial fluid and CSF. While Abeta and tau represent the two key pathological mediators of disease, other aspects of this multifaceted disease (e.g. oxidative stress, calcium-mediated toxicity, and neuroinflammation) are being unraveled, with the hope to develop a more comprehensive approach in exploring disease mechanisms. This has not only expanded possible areas for disease-modifying therapies, but has also allowed the introduction of novel, and potentially useful, fluid and radiological markers for the presence and progression of AD pathology. There is no doubt that the identification of several fluid and imaging biomarkers that can reliably detect the early stages of AD will have great implications in the design of clinical trials, in the selection of homogenous research populations, and in the assessment of disease outcomes. Markers with good diagnostic specificity will aid researchers in differentiating individuals with preclinical and probable AD from individuals who do not have AD pathology or have other dementing disorders. Markers that change with disease progression may offer utility in assessing the rates of disease progression and the efficacy of potential therapeutic agents on AD pathology. For both of these purposes, CSF Abeta42, amyloid imaging, and CSF tau appear to be very good markers of the presence of AD pathology as well as predictive of who will progress from MCI to AD. Volumetric MRI is also good at separating individuals with MCI and AD from controls and is predictive of who will progress from MCI to AD. Perhaps the most important role biomarkers will have, and the most needed at this time, lies in the identification of individuals who are cognitively normal, and yet have evidence of AD pathology (i.e. preclinical AD). Such individuals, it appears, can be identified with CSF Abeta42, amyloid imaging, and CSF tau. Such individuals are the most likely to benefit from future disease modifying/prevention therapies as they become available, and therefore represent the population in which the field can make the biggest therapeutic impact.
    Neuropharmacology 01/2010; 59(4-5):310-22. · 4.11 Impact Factor
  • Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2010; 6(4).
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    Rawan Tarawneh, David M Holtzman
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    ABSTRACT: Over the last 10 years, promising data has emerged from both animal and human studies that both active immunization with amyloid-beta (Abeta) as well as passive immunization with anti-Abeta antibodies offer promise as therapies for Alzheimer's disease (AD). Data from animal models suggests that antibodies to Abeta through several mechanisms can decrease Abeta deposition, decrease Abeta -associated damage such as dystrophic neurite formation, and improve behavioral performance. Data from human studies suggests that active immunization can result in plaque clearance and that passive immunotherapy might result in slowing of cognitive decline. Despite this, a recent analysis from a phase I trial that involved active immunization with Abeta42, while not powered to determine efficacy, suggested no large effect of active immunization despite the fact that plaque clearance was very prominent in some subjects. An important issue to consider is when active or passive immunization targeting Abeta has the chance to be most effective. Clinico-pathological and biomarker studies have shown that in terms of the time course of AD, Abeta deposition probably begins about 10-15 years prior to symptom onset (preclinical AD) and that tau aggregation in tangles and in neurites does not begin to accelerate and build up in larger amounts in the neocortex until just prior to symptom onset. By the time the earliest clinical signs of AD emerge, Abeta deposition may be close to reaching its peak and tangle formation and neuronal cell loss is substantial though still not at its maximal extent. Since immunization targeting Abeta does not appear to have major effects on tangle pathology, for immunization to have the most chance for success, performing clinical trials in individuals who are cognitively only very mildly impaired or even in those with preclinical AD would likely offer a much better chance for success. Current work with AD biomarkers suggests that such individuals can now be identified and it seems likely that targeting this population with immunization strategies targeting Abeta would offer the best chance of success.
    CNS & neurological disorders drug targets 05/2009; 8(2):144-59. · 3.57 Impact Factor
  • Rawan Tarawneh, James E Galvin
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    ABSTRACT: Lewy body dementia (LBD) is the second most common dementia after Alzheimer's disease (AD). LBD is characterized clinically by visual hallucinations, extrapyramidal symptoms, cognitive fluctuations and neuroleptic sensitivity. LBD and AD share many common features in pathology, genetics and biochemical alterations; however, correct clinical distinction between these disorders has prognostic and therapeutic implications. There are currently no definitive radiological or biological markers for LBD, but studies suggest that premorbid differences in cognitive domains and personality traits, differences in clinical presentation, and alterations in autonomic function and sleep may improve diagnosis. Cholinergic dysfunction plays a major role in both AD and LBD; however, dysfunction is greater in LBD. This may account for the more prominent hallucinations, and offers the possibility of a greater response to cholinesterase inhibitors in LBD. The treatment of LBD is symptomatic and is based on a limited number of clinical trials and extension of results from trials in AD. Current research is focused on the role of synuclein aggregation with possible roles for synuclein-derived peptides as aggregation inhibitors. Other approaches target amyloid, neuroinflammation, oxidative injury, proteolysis, lipid peroxidation and immunotherapies with variable results. Improved understanding of disease mechanisms may open new therapeutic avenues for LBD in the future.
    Expert Review of Neurotherapeutics 12/2007; 7(11):1499-516. · 2.96 Impact Factor

Publication Stats

106 Citations
43.25 Total Impact Points

Institutions

  • 2007–2012
    • University of Washington Seattle
      • Department of Neurology
      Seattle, WA, United States
  • 2009–2010
    • Washington University in St. Louis
      • Department of Neurology
      San Luis, Missouri, United States