Biology subjects

Suarez-Calvet, M.

Publications and source records attributed to Suarez-Calvet, M..

4 recordsLinked to original sources

bioRxiv2026

Cognitive Vergence and Pupillary Responses as Functional Oculomotor Signatures to Differentiate AT(N) Biological Profiles

BackgroundThe AT(N) biological framework classifies Alzheimers disease (AD) pathology using CSF biomarkers, with the A+T+ profile defining biological AD and the A-T+ profile representing a biologically distinct entity consistent with suspected non-Alzheimers pathophysiology, such as primary age-related tauopathy. Functional assessment capable of differentiating these profiles non-invasively remains limited. This study investigates whether cognitive vergence and pupillary temporal dynamics during a visual oddball task can distinguish A-T+ from A+T+ biological profiles in individuals with mild cognitive impairment (MCI). MethodsThirty-eight participants with MCI (12 A-T+, 26 A+T+) classified by CSF biomarkers completed a visual oddball task (80% distractors, 20% targets) under continuous eye-tracking. Linear mixed-effects models examined profile x condition interactions on full time series and six trial-level temporal features. Participant-level differentiation was assessed using binomial logistic regression, adjusting for age, sex, and MMSE. ResultsBoth profiles showed comparable overall oculomotor response magnitudes but diverged markedly in temporal organization. Significant profile x condition interactions emerged for cognitive vergence global slope, time to peak, and pupillary time to peak. Logistic regression confirmed that timing features discriminated biological profiles at the participant level, with differentiation reversing direction between distractor and target conditions. A-T+ participants also maintained superior target detection accuracy (89.3% vs. 82.4%, p = 0.001). ConclusionCognitive Vergence and pupillary temporal dynamics during an oddball task provide condition-dependent functional oculomotor signatures that systematically differentiate AT(N) biological profiles in MCI, suggesting that oculomotor assessment may offer an accessible, non-invasive complement to CSF-based profile characterization.

neuroscience↗

bioRxiv2026

Cognitive Vergence and Pupil Response During Oddball Task are Associated With Alzheimers Disease Cerebrospinal Fluid Neurodegenerative Biomarkers

BackgroundAlzheimers disease (AD) can be diagnosed using cerebrospinal fluid (CSF) biomarkers reflecting amyloid and tau pathology. However, it provides no information about functional network status. We aimed to determine whether CSF biomarkers (A{beta}42, p-Tau, t-Tau, and A{beta}42/p-Tau ratio) are associated with altered stimulus differentiation in vergence and pupil responses during an oddball task, and to evaluate oculomotor metrics as predictors of CSF core AD biomarkers in patients at mild cognitive impairment (MCI) stage. MethodsThirty-eight participants with abnormal CSF core AD biomarkers at MCI stage completed a visual oddball task while oculomotor responses were recorded. Linear mixed-effects models examined condition x biomarker interactions, controlling for sex, age, and MMSE. Temporal and magnitude features were tested as predictors using linear regression. ResultsHigher p-Tau levels were negatively associated with target-distractor differentiation in cognitive vergence ({beta} = -0.035, p < 0.001) and pupil responses ({beta} = - 0.060, p < 0.001). Higher A{beta}42 and A{beta}42/p-Tau showed positive associations with vergence differentiation but opposite effects on pupil responses. Oculomotor features predicted p-Tau levels (R2 = 0.20-0.21). ConclusionOculomotor differentiation metrics capture functional signatures of tau-related network dysfunction, positioning them as accessible biomarkers complementing CSF measures for detecting network disruption at MCI stage.

neuroscience↗

bioRxiv2024

Enhanced proteome profiling of human cerebrospinal fluid using a commercial plasma enrichment strategy

Cerebrospinal fluid (CSF) is a valuable liquid biopsy for identifying protein biomarkers in neurological diseases, yet its proteome profiling faces challenges due to the large dynamic range of protein abundances. In this study, we assessed the effectiveness of a commercial enrichment strategy, initially developed for plasma samples, in enhancing the detection of low-abundance proteins in human CSF. We demonstrate significant improvements in protein identification and coverage depth while maintaining high reproducibility and low coefficients of variation. These findings underscore the potential of this enrichment strategy to facilitate rapid and sensitive CSF analysis, advancing biomarker discovery in neurological research.

molecular biology↗

bioRxiv2018

The MS4A gene cluster is a key regulator of soluble TREM2 and Alzheimer disease risk

Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels in the cerebrospinal fluid (CSF) have been associated with Alzheimer disease (AD) status. TREM2 plays a critical role in microglial activation, survival, and phagocytosis; however, the pathophysiological role of sTREM2 in AD is not well understood. Understanding the role of sTREM2 in AD may help reveal biological mechanisms underlying AD and identify novel therapeutic targets. We performed a genome-wide association study (GWAS) to identify genetic modifiers of CSF sTREM2 levels. Common variants in the membrane-spanning 4-domains subfamily A (MS4A) gene region were associated with higher CSF sTREM2 levels (rs1582763; P = 1.15x10-15) and replicated in independent datasets. The variants associated with increased levels of sTREM2 are also associated with reduced AD risk and delayed age-at-onset. Rs1582763 influences expression of MS4A4A and MS4A6A in multiple tissues, suggesting that one or both of these genes are important for regulating sTREM2. MS4A genes encode transmembrane proteins that may play a role in intracellular protein trafficking in microglia. We used human macrophages to begin to test the relationship between MS4A4A and TREM2 and found that they co-localize intracellularly and that antibody-mediated targeting of MS4A4A reduces sTREM2. Thus, genetic, molecular, and cellular findings suggest that MS4A4A regulates sTREM2. These findings also provide a mechanistic explanation of the original GWAS signal in the MS4A locus for AD risk and indicate that TREM2 is involved in sporadic AD risk in general, not only in TREM2 risk-variant carriers.

genomics↗