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AChems Press Release
Press Abstracts
#220
Genome-wide Association Study Meta-analysis of Dietary Intake in Two Cohorts Identifies Seven Novel Olfactory Receptor Associations
Joanne Cole1, Maizy Brasher1, Franco Giulianini2, Daniel Chasman2
1Department of Biomedical informatics, University of Colorado School of Medicine, Aurora, CO, USA
2 Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA
Genome-wide association studies (GWAS) of food liking and intake have identified hundreds of genetic associations, including loci near several olfactory and taste receptor genes. These represent an important first step in understanding how smell and taste perception shape preferences, behavior, and health. To identify more novel associations between dietary intake and taste and olfactory receptor loci, we performed GWAS meta-analysis of 38 self-reported dietary intake traits (e.g., beef, bread, cheese, coffee, tea, vegetables, fruit, fish, and alcohol) in ~450K individuals in UK Biobank and ~23K females in Women's Genome Health Study. GWAS were conducted in European ancestry and adjusted for age, sex (UK Biobank only), center/location, and ancestry via principal components. Association results were interrogated across 788 olfactory receptor genes, including pseudogenes, downloaded from The Human Olfactory Data Explorer and a manually curated set of 36 taste-related genes (including 27 taste receptors). Novel loci were defined as genome-wide significant (P<5x10-8) and independent (R2<0.10) from loci reported in the previous UK Biobank-only diet GWAS. We identified seven novel olfactory receptor loci associated with diet. Three loci, nearest OR52K1, OR52N4, OR1F1, were associated with raw and cooked vegetable intake. While OR1F1 odorants overlap plant-derived volatiles, little is known about the functional roles of OR52K1 and OR52N4. Additional associations were observed for beef intake (near OR6B3 and OR2V2), fish intake (near OR7E160P), and fruit intake (OR4S1). These findings extend prior diet GWAS associations to include novel olfactory receptor loci, highlighting promising targets for downstream functional characterization and assessment of their role in eating behavior.
#50
Alzheimer's pathobiology detection prior to symptom onset via olfactory biopsy analysis
Vincent M D'Anniballe1, Bradley J Goldstein2
1Duke Medical Scientist Training Program, Duke University School of Medicine, Durham, NC, USA,
2Department of Head and Neck Surgery & Communication Sciences, Duke University School of Medicine, Durham, NC, USA
Early detection of Alzheimer's disease (AD) before cognitive decline remains a critical unmet need. Current diagnostics rely on amyloid-β and p-tau measurements in plasma or cerebrospinal fluid, rather than direct interrogation of living neuronal tissue. This limitation may obscure early pathogenic mechanisms, constrain functional assays, and contribute to ongoing debate regarding the biological relevance of observed pathology. Similar to cortical neurons at advanced disease stages, olfactory sensory neurons (OSNs) in the nasal olfactory epithelium (OE) accumulate hallmark AD pathology. However, whether detectable pathobiology impacts the peripheral OE at an early, pre-clinical stage has remained unclear. We performed endoscopically guided OE brush biopsies in adults classified by 2024 Alzheimer's Association biomarker criteria as controls (n=6), asymptomatic pre-clinical AD (n=9), or clinical AD (n=6). Single-cell RNA sequencing profiled live OE cells using experimentally validated gene expression programs, flow cytometry provided orthogonal validation. Strikingly, pre-clinical OSNs exhibited inflammatory programs previously described in postmortem AD cortical neurons. OE myeloid cells adopted an inflammatory, microglia-like state that intensified with disease progression. Concurrently, OE CD8⁺ memory T cells exhibited elevated antigen-specific activation scores in pre-clinical AD compared with controls, mirroring cerebrospinal fluid T cell activation in clinical AD, and confirmed by increased CD38⁺HLA-DR⁺CD8⁺ T cells by flow cytometry. Together, these findings support OE brush biopsies as a minimally invasive approach to capture neuronal and immune signatures of AD prior to cognitive impairment, supporting use for early detection and mechanistic discovery.
#106
Position-Specific Olfactory Signature Among Former Professional American-styleFootball Players
Benoit Jobin1,2, Colin Magdamo1,2, Rachel Grashow3,4, Michael Leung3,4, Ona Wu1,2,5 Jacob Dodelson1,2,5, Grant Iverson1,2,6, Marc Weisskopf3,4, Ross Zafonte1,2,6, Aaron Baggish1, Mark Albers1,2
1Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
2Harvard Medical School, Boston, MA, USA
3Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA
4The Football Players Health Study at Harvard University, Harvard Medical School, Boston, MA, USA
5Athinoula A Martinos Center for Biomedical Imaging, Charlestown, MA, USA
6Spaulding Rehabilitation Hospital, Charlestown, MA, USA
Olfactory deficits are well documented after traumatic brain injury, yet the integrity of the central olfactory system has not been characterized in former professional athletes exposed to repetitive head impacts. This study examined which aspects of American-style football (ASF) exposure relate to olfactory function and central olfactory system morphometry. We analyzed data from 91 former professional ASF players participating in the Football Players Health Study at Harvard University. All individuals completed a comprehensive olfactory assessment including odor discrimination (OD10), identification (OPID18), and recognition memory, and underwent structural MRI. T1-weighted MRI scans were processed with FreeSurfer to quantify volumes and cortical thickness within olfactory regions. ASF exposure variables included retrospectively reported concussion signs and symptoms, primary playing position, and years of professional and non-professional play. Participants (mean age = 49.43 ± 7.86 years; 54% Black) who played lineman positions exhibited significantly lower OD10 scores than non-linemen (p = .049) and odor identification scores (p = .02), after adjusting for age and race. Lineman status moderated the relationship between thalamic volume and odor discrimination: larger thalamic volume was associated with better discrimination among non-linemen (p = .005), but not in linemen (p = .80). Mediation analyses showed that thalamic volume did not account for the link between lineman status and OD10 score. The lineman position was negatively associated with odor discrimination, identification, and altered thalamic-function relationships. Position related exposures may differentially affect central olfactory pathways, although other mechanisms likely contribute to the observed deficits.
#77
A New Tool to Identify and Pharmacologically Characterize GLP-1 Stimuli
Valentina Casà, Sara Montelatici, Laura Stucchi, Camilla Trovesi, Paola Bonetti, Stefania De Cesare, Alice Segnali, Loredana Redaelli, Viviana Agus, Alberto Di Silvio, Marcel Winnig
Axxam SpA, Milan, Italy
Enteroendocrine cells, comprising about 1% of the intestinal epithelium, are specialized cells that sense nutrients and mediate hormone secretion. Among them, enteroendocrine L-cells are responsible for secreting Glucagon-like Peptide-1 (GLP-1), which is essential for regulating appetite and glucose metabolism. GLP-1 promotes insulin secretion from the pancreas, suppresses appetite and contributes to weight loss. To detect GLP-1 secretion from enteroendocrine cell supernatants, we optimized and validated a GLP-1 secretion assay. We employed NCI-H716 and STC-1 cell lines, well-characterized models for human and murine intestinal L-cells, respectively, along with a reporter cell line that expresses the recombinant GLP-1 Receptor in combination with the chAMPion reporter system. Our high-throughput screening (HTS)-grade GLP-1 secretion assay was functionally assessed using carbohydrate stimuli, including fructose. Additionally, by testing specific receptor agonists, we confirmed a role for Bitter Taste Receptor 38 (TAS2R38) and Free Fatty Acid Receptor 4 (FFAR4, also known as GPR120) in stimulating GLP-1 release from NCI-H716 and STC-1 cells, respectively. In conclusion, we developed a powerful tool for identifying and pharmacologically profiling novel GLP-1 stimuli, demonstrating its applicability for the identification of new therapeutic strategies in the treatment of diabetes and obesity.
#65
AChemS Undergrad Finalist: Sex-Dependent Estrogenic Regulation of Peripheral Fat Taste Signaling
Kaylee Perez1,2, Emeline Masterson1,2, Eloisa Grajales1, Caroline Ferrarin1, Timothy A. Gilbertson2
1Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA
2Medicine, University of Central Florida, Orlando, FL, USA
Recent work demonstrates sex differences in dietary fat perception and preference, yet the cellular mechanisms underlying these differences remain poorly understood. Estrogen influences feeding behavior, but its role in peripheral fat taste signaling remains incomplete. Expression studies indicate that estrogen receptors, including estrogen receptor alpha (ERα) and the G protein-coupled estrogen receptor 1 (GPER1), are present in taste receptor cells (TRCs) and may modulate fatty acid-evoked signaling pathways. To investigate estrogen's contribution to fatty acid taste transduction, we employed a multidisciplinary approach that combined ovariectomy, ratiometric calcium imaging, and pharmacological interventions in genetically identifiable taste cell populations. Intracellular calcium responses to long-chain polyunsaturated fatty acids were examined in isolated taste cells from male mice and from intact and ovariectomized female mice. Transgenic mouse lines expressing GFP-PLCβ2 and GFP-GAD67 were used to distinguish Type II and Type III TRCs, respectively, enabling cell-type-specific analysis of estrogenic modulation. We hypothesized that estrogen deprivation alters fatty acid-evoked calcium signaling in TRCs, primarily through effects on Type II cells. Our results indicate that estrogen significantly modulates fatty acid-evoked responses in Type II TRCs via the TRPM4/TRPM5 signaling pathway. Additionally, loss of estrogen following ovariectomy disrupts the function of key fatty acid signaling components, including calcium-release activated calcium channels and CD36, in a sex-dependent and cell-type-specific manner. Together, these findings elucidate how estrogen shapes peripheral fat taste signaling and provide mechanistic insight into sex-specific differences in dietary fat perception and intake.
#146
Novel 3D printed "Smell-Aids" to improve olfactory function in post COVID-19 era
Joanne Xu, Lauren Gastineau, Kanghyun Kim, Nidhi Jha, Kai Zhao
Department of Otolaryngology - Head & Neck Surgery, the Ohio State University, Columbus, OH, USA
We previously invented non-invasive "Smell-Aids" to improve olfactory function by enhancing intranasal odorant delivery to the olfactory epithelium. However, the initial design was hand-made foam nasal plugs, lacking professional appearance, consistency, and scalability. Here, we attempted to update the prototype fabrication using 3D printing. 2 plug sizes were designed to accommodate different nostril sizes, each incorporating diagonal airflow channels of either small (5mm) or large (7mm) diameters. These updated designs were then 3D printed using the Formlabs Form 3 SLA printer with Silicon 40A photopolymer resin. We tested the prototypes in counter-balanced orders on 18 patients with confirmed olfactory losses (age 19-89y, median=62), majority of whom (11/18=61%) were non-COVID smell losses spanning 3m-19 years. The remaining were post-COVID long haulers (n=7; infected 11/26/20 to 3/11/24; persisted 10 to 61 months, median=52m). All patients achieved comfortable fit with at least one plug size. The 9-item NIH toolbox odor identification score significantly improved with the large channel (7mm) in the upward direction (baseline: 3.2±1.99 vs plug: 4.0±2.03, p<0.05), especially among the non-COVID cohort (2.6±1.99 to 3.6±2.03, p<0.05). No significant improvement was observed with the plug downward direction nor with small diameter plugs. Subgroup analysis on patients who reported distorted smell (parosmia/phantosmia 4/18) showed no significant effect. These results further demonstrated the promise of improving olfactory function through peripheral mechanisms with efficacy depending on the amount of air/odor flow (large channel) redirected to the olfactory region and different patient cohorts.
#160
GLP-1 Receptor Agonists Significantly Impair Taste Function
Essi Hantikainen1, Roberto Melotti1, Martin Gögele1, Peter Pramstaller1, Christian Fuchsberger1, Johannes Frasnelli2,3,4
11Institute for Biomedicine, Eurac Research, Bolzano, Italy
2Department of Anatomy, Universite du Quebec a Trois-Rivieres, Trois-Rivières, QC, Canada
3Research Center, Sacre-Coeur Hospital, Montréal, QC, Canada
4Research Center, Institut universitaire de Geriatrie de Montreal, Montréal, QC, Canada
Olfactory dysfunction is associated with increased all-cause mortality among older adults and an early indicator of brain aging. Different lifestyle factors and health conditions determine olfactory function, however, there is limited knowledge on the association with diet quality. We investigated the association between various dietary patterns and olfactory function, as well as hyposmia, in a general population study using cross-sectional data from more than 6000 participants of the Cooperative Health Research in South Tyrol (CHRIS) study. We assessed self-reported dietary intake through the GA2LEN semi-quantitative Food Frequency questionnaire, which was used to derive five established dietary pattern indices (Alternate Healthy Eating Index 2010, Mediterranean diet index, Plant-based dietary index, Healthy Plant-based dietary index, Unhealthy plant-based dietary index), as well as various food groups. Olfactory function was measured through the Sniffin'Sticks odor identification test, which allowed us to determine hyposmia with a score >12/16. Multivariable ordinal and logistic regression models were fitted to investigate associations between each dietary pattern, food groups and olfaction. Higher adherence to all healthy dietary patterns was associated with both better olfactory function and lower rates of hyposmia, while the opposite was observed for the unhealthy plant-based diet. Specifically, higher consumption of fruits, vegetables, coffee and tea was beneficially associated with both outcomes. Higher adherence to healthy dietary patterns that are rich in plant-based foods was associated with better olfactory function and lower rates of hyposmia.
#86
Peripheral Gustatory Degeneration Contributes to Taste Dysfunction in Mouse Models of Alzheimer's Disease
Tao Tang, Brian Pierchala
Indiana University School of Medicine, Indianapolis, IN, USA
Malnutrition and weight loss are common comorbidities of Alzheimer's disease (AD) and are strongly associated with functional decline and increased mortality. Taste dysfunction is frequently reported in AD patients and can precede cognitive symptoms, yet its biological basis remains poorly understood. Most studies have focused on central nervous system degeneration while largely overlooking the potential role of dysfunction peripheral gustatory system. We examined whether AD pathology disrupts peripheral taste structures and their sensory innervation using three neuropathologically distinct mouse models of AD: the 5XFAD amyloid model, the PS19 tauopathy model, and the LOAD2 late-onset AD model, across multiple disease stages. Analysis of fungiform taste buds and geniculate ganglion-derived innervation revealed significantly age- and sex-dependent deficits. In 12-month-old 5XFAD mice, taste bud numbers were reduced in both sexes, whereas taste bud volume loss and reductions in TUJ1+ and PHOX2B+ innervation were observed only in females. In the PS19 model, no changes were detected at 6 months of age. At 9 months, however, PHOX2B+ innervation was selectively reduced without alterations in total innervation or taste bud number. In 12-month-old LOAD2 mice, taste bud number, taste bud volume, and sensory innervation were all significantly reduced. Together, these findings demonstrate that AD is associated with progressive degeneration of peripheral taste buds and their sensory innervation, suggesting that peripheral gustatory dysfunction may contribute to impaired taste perception, appetite dysregulation, and weight loss in AD.
#197
Vector-based taste representations of food odours predict appetitive value
Putu A Khorisantono1, Apostolia Filippopoliti1, Maria G Veldhuizen2,3 Janina Seubert1
1Karolinska Institutet, Solna, Sweden
2Mersin University, Mersin, Turkey
3Bilkent University, Ankara, Turkey
Flavour perception arises from the integration of gustatory and olfactory signals, yet how learned taste-odour associations are represented in the brain and translated into appetitive behaviour remains poorly understood. Our prior work demonstrated that aromas acquire taste-like neural representations through flavour learning: using a flavour-binding paradigm and fMRI, we showed that tasteless aromas evoke activity patterns in the human insular cortex that overlap with those elicited by their paired tastants, particularly in the dysgranular and agranular insula. These findings established a shared and dynamic neural code for taste and retronasal olfaction, providing a cortical mechanism through which aromas acquire consummatory meaning. Building on this neural framework, the present pre-registered study extends taste-odour integration beyond retronasal perception to orthonasal food odours and examines how predicted taste properties modulate food wanting. Healthy volunteers completed a taste-rating session to derive individual sweet and savoury preference, followed by ratings of orthonasally delivered food odours along sweetness, savouriness and wanting dimensions. Mixed-effects modelling predicted odour-elicited food wanting from an interaction between individual taste liking and the expected taste properties of food odours. Moreover, a vector-based representation of odours in sweet-savoury space outperformed a scalar spectral model in predicting appetitiveness, with cross-validated generalisation across participants. Together, these findings link shared taste-odour neural coding in the insula to orthonasal odour-guided appetitive behaviour, highlighting how lifelong associative learning shapes food valuation and suggesting mechanisms through which sensory expectations influence dietary choices.
