Browsing by Author "Jicha, Gregory A."

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    Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy
    (Springer, 2016-01) Kovacs, Gabor G.; Ferrer, Isidro; Alafuzoff, Irina; Attems, Johannes; Budka, Herbert; Cairns, Nigel J.; Crary, John F.; Duyckaerts, Charles; Ghetti, Bernardino; Halliday, Glenda M.; Ironside, James W.; Love, Seth; Mackenzie, Ian R.; Munoz, David G.; Murray, Melissa E.; Nelson, Peter T.; Takahashi, Hitoshi; Trojanowski, John Q.; Ansorge, Olaf; Arzberger, Thomas; Baborie, Atik; Beach, Thomas G.; Bieniek, Kevin F.; Bigio, Eileen H.; Bodi, Istvan; Dugger, Brittany N.; Feany, Mel; Gelpi, Ellen; Gentleman, Stephen M.; Giaccone, Giorgio; Hatanpaa, Kimmo J.; Heale, Richard; Hof, Patrick R.; Hofer, Monika; Hortobágyi, Tibor; Jellinger, Kurt; Jicha, Gregory A.; Ince, Paul; Kofler, Julia; Kövari, Enikö; Kril, Jillian J.; Mann, David M.; Matej, Radoslav; McKee, Ann C.; McLean, Catriona; Milenkovic, Ivan; Montine, Thomas J.; Murayama, Shigeo; Lee, Edward B.; Rahimi, Jasmin; Rodriguez, Roberta D.; Rozemüller, Annemieke; Schneider, Julie A.; Schultz, Christian; Seeley, William; Seilhean, Danielle; Smith, Colin; Tagliavini, Fabrizio; Takao, Masaki; Thal, Dietmar Rudolf; Toledo, Jon B.; Tolnay, Markus; Troncoso, Juan C.; Vinters, Harry V.; Weis, Serge; Wharton, Stephen B.; White III, Charles L.; Wisniewski, Thomas; Woulfe, John M.; Yamada, Masahito; Dicks, Dennis W.; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.
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    Alzheimer's disease and inflammatory biomarkers positively correlate in plasma in the UK‐ADRC cohort
    (Wiley, 2024) Foley, Kate E.; Winder, Zachary; Sudduth, Tiffany L.; Martin, Barbara J.; Nelson, Peter T.; Jicha, Gregory A.; Harp, Jordan P.; Weekman, Erica M.; Wilcock, Donna M.; Neurology, School of Medicine
    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. Statistics were performed to assess correlations. Results: Our large cohort reflects previous plasma biomarker findings. Relationships between biomarkers to understand AD-inflammatory biomarker correlations showed significant associations between AD and inflammatory biomarkers suggesting peripheral inflammatory interactions with increasing AD pathology. Biomarker associations parsed out by clinical diagnosis (normal, MCI, and dementia) reveal changes in strength of the correlations across the cognitive continuum. Discussion: Unique AD-inflammatory biomarker correlations in a community-based cohort reveal a new avenue for utilizing plasma-based biomarkers in the assessment of AD and related dementias. Highlights: Large community cohorts studying sex, age, and APOE genotype effects on biomarkers are few. It is unknown how biomarker-biomarker associations vary through aging and dementia. Six AD (Aβ40, Aβ42, Aβ42/40, p-tau181, total tau, and NfLight) and five inflammatory biomarkers (TNFα, IL6, IL8, IL10, and GFAP) were used to examine associations between biomarkers. Plasma biomarkers suggesting increasing cerebral AD pathology corresponded to increases in peripheral inflammatory markers, both pro-inflammatory and anti-inflammatory. Strength of correlations, between pairs of classic AD and inflammatory plasma biomarker, changes throughout cognitive progression to dementia.
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    Associations of Future Cognitive Decline with Sexual Satisfaction among Married Older Adults
    (Taylor & Francis, 2021) Smith, Allison G.; Bardach, Shoshana H.; Barber, Justin M.; Williams, Andrea; Rhodus, Elizabeth K.; Parsons, Kelly K.; Jicha, Gregory A.; Psychiatry, School of Medicine
    Objectives: This study sought to explore changes in longitudinal cognitive status in relation to baseline measures of intimacy and sexuality in cognitively intact, married older adults. Methods: Baseline intimacy and sexuality survey data from 155, cognitively intact, married, older adults were collected using a novel survey instrument that explored the domains of: 1) romance with one's partner, 2) sexual satisfaction, 3) beliefs about sexuality, and 4) social support and emotional intimacy. These data were analyzed in relation to change in cognitive status over a 10-year follow-up period using binary logistic regression modeling. Exploratory factor analysis was used to assess the shared variance of survey items attributable to intimacy and sexuality without specification of an a priori hypothesis regarding the association of intimacy and sexuality with future change in cognitive status. Results: Over the 10-year study period, 33.5% (n = 52) of individuals developed cognitive impairment. Participants with greater sexual satisfaction scores at baseline were statistically less likely to convert from cognitively intact to mild cognitive impairment or dementia in the future (p = .01). The domains of romance with one's partner, beliefs about sexuality, and social support/emotional intimacy were not predictive of future longitudinal changes in cognitive status. Conclusions: Sexual satisfaction is associated with longitudinal cognitive outcomes in cognitively intact, married, older adults. Clinical implications: Clinicians should routinely assess for sexual satisfaction among older adults and refer to appropriate providers, such as couples or sex therapists, when appropriate.