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Erik D Roberson

Publications and source records attributed to Erik D Roberson.

7 recordsLinked to original sources
PubMed2026

Interconnected influences of diet, gut microbiome, and metabolome on cognition across three metabolomics platforms.

Cognitive impairment is increasing with global aging, yet mechanisms linking diet, the gut microbiome, and metabolism to cognitive function remain unclear. To investigate a diet-microbiome-metabolome axis associated with cognition, we integrated fecal metagenomics, diet, and multi-platform plasma metabolomics in 505 older adults from four ADRCs. Several microbes broadly associated with circulating metabolites were also linked to multiple measures of cognitive performance. These taxa exhibited coordinated metabolic signatures, with cognition-positive microbes associated with antioxidant, lipid, and microbial-host co-metabolites, and microbes negatively associated with cognition were linked to inflammatory and aromatic amino acid-derived metabolites. Dietary patterns, particularly the Healthy Eating Index Greens and Beans component, were associated with microbial composition and metabolomic structure. Mediation analyses supported a diet-microbe-metabolite-cognition pathway, while metabolites remained associated with cognition after accounting for microbial features. These findings highlight the metabolome as a central integrator of diet, microbial activity, and cognitive function.

Journal Article↗
PubMed2025

Comprehensive cross-sectional and longitudinal comparisons of plasma glial fibrillary acidic protein and neurofilament light across FTD spectrum disorders.

BACKGROUND: Therapeutic development for frontotemporal dementia (FTD) is hindered by the lack of biomarkers that inform susceptibility/risk, prognosis, and the underlying causative pathology. Blood glial fibrillary acidic protein (GFAP) has garnered attention as a FTD biomarker. However, investigations of GFAP in FTD have been hampered by symptomatic and histopathologic heterogeneity and small cohort sizes contributing to inconsistent findings. Therefore, we evaluated plasma GFAP as a FTD biomarker and compared its performance to that of neurofilament light (NfL) protein, a leading FTD biomarker. METHODS: We availed ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources to conduct a comprehensive cross-sectional and longitudinal examination of the susceptibility/risk, prognostic, and predictive performance of GFAP and NfL in the largest series of well-characterized presymptomatic FTD mutation carriers and participants with sporadic or familial FTD syndromes. Utilizing single molecule array technology, we measured GFAP and NfL in plasma from 161 controls, 127 presymptomatic mutation carriers, 702 participants with a FTD syndrome, and 67 participants with mild behavioral and/or cognitive changes. We used multivariable linear regression and Cox proportional hazard models adjusted for co-variates to examine the biomarker utility of baseline GFAP and NfL concentrations or their rates of change. RESULTS: Compared to controls, GFAP and NfL were elevated in each FTD syndrome but GFAP, unlike NfL, poorly discriminated controls from participants with mild symptoms. Similarly, both baseline GFAP and NfL were higher in presymptomatic mutation carriers who later phenoconverted, but NfL better distinguished non-converters from phenoconverters. We additionally observed that GFAP and NfL were associated with disease severity indicators and survival, but NfL far outperformed GFAP. Nevertheless, we validated findings that the GFAP/NfL ratio may discriminate frontotemporal lobar degeneration with tau versus TDP-43 pathology. CONCLUSIONS: Our head-to-head comparison of plasma GFAP and NfL as biomarkers for FTD indicate that NfL consistently outmatched GFAP as a prognostic and predictive biomarker for participants with a FTD syndrome, and as a susceptibility/risk biomarker for people at genetic risk of FTD. Our findings underscore the need to include leading biomarkers in investigations evaluating new biomarkers if the field is to fully ascertain their performance and clinical value.

Humans↗
PubMed2006

100 years and counting: prospects for defeating Alzheimer's disease.

This week marks a century since the first description of Alzheimer's disease (AD). Despite approval of several drugs for AD, the disease continues to rob millions of their memories and their lives. Fortunately, many new therapies directly targeting the mechanisms underlying AD are now in the pipeline. Among the investigative AD therapies in clinical trials are several strategies to block pathogenic amyloid-beta peptides and to rescue vulnerable neurons from degeneration. Complementary but less mature strategies aim to prevent the copathogenic effects of apolipoprotein E and the microtubule-associated protein tau. New insights into selective neuronal vulnerability and the link between aging and AD may provide additional entry points for therapeutic interventions. The predicted increase in AD cases over the next few decades makes the development of better treatments a matter of utmost importance and urgency.

Alzheimer Disease↗
PubMed2006

Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease.

Alzheimer's disease (AD) may result from the accumulation of amyloid-beta (Abeta) peptides in the brain. The cysteine protease cathepsin B (CatB) is associated with amyloid plaques in AD brains and has been suspected to increase Abeta production. Here, we demonstrate that CatB actually reduces levels of Abeta peptides, especially the aggregation-prone species Abeta1-42, through proteolytic cleavage. Genetic inactivation of CatB in mice with neuronal expression of familial AD-mutant human amyloid precursor protein (hAPP) increased the relative abundance of Abeta1-42, worsening plaque deposition and other AD-related pathologies. Lentivirus-mediated expression of CatB in aged hAPP mice reduced preexisting amyloid deposits, even thioflavin S-positive plaques. Under cell-free conditions, CatB effectively cleaved Abeta1-42, generating C-terminally truncated Abeta peptides that are less amyloidogenic. Thus, CatB likely fulfills antiamyloidogenic and neuroprotective functions. Insufficient CatB activity might promote AD; increasing CatB activity could counteract the neuropathology of this disease.

Age Factors↗
PubMed2006

Frontotemporal dementia.

Frontotemporal dementia (FTD) and related conditions are often considered daunting because of the numerous inter-related clinical syndromes and their apparently heterogeneous pathologic substrates. Although the labyrinthine complexity of the disease seemingly continues to grow, recent discoveries have made the maze of FTD somewhat more navigable, spurring new interest in the field. This review begins by surveying the fascinating clinical presentations of these conditions and the few currently available treatments, then turns to recent progress in understanding the pathophysiology of FTD. Among the important advances surveyed are clinicopathologic correlations that enable prediction of the pathologic substrate of certain clinical subtypes, and genetic studies that have been particularly fruitful in identifying new causes of FTD.

Dementia↗
PubMed2005

Frontotemporal lobar degeneration: demographic characteristics of 353 patients.

BACKGROUND: Until recently, frontotemporal lobar degeneration (FTLD) was considered a rare neurodegenerative disorder that was difficult to diagnose. The publication of consensus criteria for FTLD, however, prompted systematic studies. The criteria categorize FTLD into 3 subgroups: frontotemporal dementia, semantic dementia, and progressive nonfluent aphasia. OBJECTIVE: To compare demographic characteristics of patients in the 3 FTLD subgroups. DESIGN: We compared diagnostic breakdown, age at onset, sex, Mini-Mental State Examination score at first visit, education, and neuropathological diagnoses in a large sample of FTLD patients from 3 different university dementia clinics, including 2 neurologic clinics in the United States and 1 psychiatric clinic in Germany. RESULTS: The frontotemporal dementia subgroup represented approximately half of all FTLD diagnoses. Patients diagnosed as having frontotemporal dementia (mean age, 57.5 years) and semantic dementia (mean age, 59.3 years) had an earlier age at onset than patients diagnosed as having progressive nonfluent aphasia (mean age, 63.0 years). There were significantly more men diagnosed as having frontotemporal dementia (63.5%) and semantic dementia (66.7%) when compared with progressive nonfluent aphasia (39.1%) (P = .005 for frontotemporal dementia vs progressive nonfluent aphasia and P = .002 for semantic dementia vs progressive nonfluent aphasia). Generally, the demographic features and diagnostic categories of the patient populations across the 3 sites were comparable. There were 68 deaths and 37 autopsies. Frontotemporal lobar degeneration with ubiquitin-positive tau-negative inclusions (48.5%), dementia lacking distinctive histopathological features (18.2%), and Pick disease (15.2%) were the most common neuropathological diagnoses. CONCLUSIONS: These findings show that cohorts of patients can be combined using new research criteria for FTLD and demonstrate striking demographic differences among FTLD subgroups. The sex and age-at-onset differences suggest that there may be biological differences among FTLD subgroups. In this sample, FTLD with ubiquitin-positive inclusions accounted for half of all neuropathological diagnoses.

Adult↗