Aug 2026· Theoretical and Natural Science· Vol 184, pp. 227-232· 0 citations
TL;DR
Study shows the non-rapid eye movement spindle and slow oscillation activity are predictive and non-invasive biomarkers for AD, and the disruption of spindle-SO coupling is associated with Aβ deposits of AD.
Abstract
Alzheimer's disease (AD) is becoming more common and putting serious pressure on global health. Current Amyloid-β (Aβ) deposition and tau protein hyperphosphorylation are two main biomarkers of AD. Clinical diagnostic approaches depend on invasive detection of amyloid-β (Aβ) deposition and tau protein hyperphosphorylation through cerebrospinal fluid (CSF) analysis, positron emission tomography (PET) imaging or blood-based biomarker (BBM) testing. Evidence showed by recent studies have identified that slow-wave-sleep spindle coupling as potential non-invasive biomarkers of neurodegeneration for AD patients. Yet, the causality between spindle disruption and cognitive decline remains unknown. This paper examines the evidences from human, rodent models, and nonhuman primate (NHP) models of recent studies. This study presents how slow wave-spindle coupling reflects prefrontal-hippocampal, thalamocortical function. And it evaluates the contributions of NHPs researches for understanding the causal mechanisms. The findings provide supportive evidence that slow-wave-spindle activity is a reliable marker of thalamocortical integrity and prefrontal-hippocampal function correlating with cognitive decline for AD. Study shows the non-rapid eye movement (NREM) spindle and slow oscillation (SO) activity are predictive and non-invasive biomarkers for AD. The disruption of spindle-SO coupling is associated with Aβ deposits of AD. This predictive biomarker of AD points toward future directions for early detection and clinical interventions. These findings enable standardized predictive detection, home-based electroencephalography (EEG) monitoring and closed-loop stimulation techniques that could strengthen the clinical translation.
A stratified approach based on amyloid status is essential for the optimal application of blood-based biomarkers in monitoring disease progression and evaluating therapeutic efficacy in future clinical trials and precision medicine.
Keun You Kim, Hyunsun Ham, E. Yoon et al.· The journal of prevention of...· 0 citations
Canine Cognitive Dysfunction (CCD) is a naturally occurring neurodegenerative syndrome in aging dogs that shares clinical and neuropathological parallels with Alzheimer’s disease (AD). As the demand for objective diagnostic tools grows, identifying reliable biofluid biomarkers is essential for clinical staging and therapeutic monitoring. This review synthesizes evidence on cerebrospinal fluid (CSF) and blood-based biomarkers (BBM) of CCD, focusing on amyloid-β (Aβ), neurofilament light chain (NfL), tau, and glial fibrillary acidic protein (GFAP). Evidence shows that Aβ42 and Aβ42/Aβ40 ratios exhibit stage-dependent, non-linear alterations resembling early compensatory phases in human AD. In contrast, tau pathology in CCD consists mainly of pre-tangle synaptic hyperphosphorylation rather than abundant neurofibrillary tangles, limiting its current diagnostic utility. GFAP, a marker of astroglial activation, shows inconsistent associations with cognitive decline and remains exploratory. Conversely, NfL has emerged as the most robust biomarker; CSF and plasma NfL levels consistently increase with age, correlate with cognitive impairment, and reflect central axonal pathology, making it the leading candidate for staging and monitoring disease progression. Overall, the CCD biomarker landscape supports a multimodal approach integrating Aβ dysregulation, axonal injury, and glial activation. Advancing this field requires harmonized diagnostic criteria, standardized sampling, and longitudinal studies. Such efforts will strengthen the translational value of CCD as a model for human dementia, accelerating discovery and therapeutic development across species.
Klysse Assumpção Barbosa, Heloísa Máximo Ribeiro, L. Benevenuto et al.· Veterinary research communic...· 0 citations
As the world’s population ages, Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is becoming more common. The current diagnoses for AD are not precise enough to identify the disorder when it is possible to cure. An early indicator of Alzheimer’s is the assessment of beta-amyloid by positron emission tomography (PET) score, a substantial decrease in the brain’s metabolomics. Furthermore, Metabolomics can be detected by UPLC (ultra-high pressure liquid chromatography). This study investigates the link between metabolic profiles and beta-amyloid load in AD in order to shed light on possible biomarkers for disease progression. The data from 59 people who have been diagnosed with moderate cognitive impairment (MCI) is extracted from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). This study uses ultra-high-performance liquid chromatography (UPLC) to investigate the correlation between baseline metabolic data and changes in amyloid PET scores. Seven metabolites, including DOPA, Methionine Sulfoxide (Met.SO), Tryptophan Betaine, choline, leucine, valine, and FA (18:2), seem to have a substantial connection with amyloid PET scores. These can be used as early indications of AD progression, especially Met.SO is particularly relevant when considering time interaction. Understanding the metabolic alterations associated with amyloid load can pave the way for future research incorporating metabolites into a therapeutic treatment that can be identified as crucial to the illness’s progression.
Marjan Falahati, Elham Ramezannejad, Yosra Vaez-Gharamaleki et al.· Research Square· 0 citations
INTRODUCTION
Alzheimer's disease (AD) is a clinical-biological entity in which pathophysiological changes precede symptoms by years. Biomarkers are essential for early and accurate diagnosis, particularly in the era of disease-modifying therapies requiring biological confirmation. Cerebrospinal fluid (CSF) and amyloid positron emission tomography (amyloid-PET) are the reference standards, but increasing attention is devoted to blood-based biomarkers (BBMs) due to their scalability and cost-effectiveness.
AREAS COVERED
In this critical perspective, the authors critically appraise the current evidence supporting plasma phosphorylated tau at threonine 217 (p-tau217) as the leading BBM for AD. They also discuss its analytical performance, biological rationale, and diagnostic accuracy across the AD continuum, its relationship with established CSF, PET, and neuropathological biomarkers, its potential role in identifying patients eligible for disease-modifying therapies, and the main clinical and biological factors influencing its interpretation. Finally, they highlight current limitations, unresolved challenges, and give their future perspectives for the integration of plasma biomarkers into routine clinical practice.
EXPERT OPINION
BBMs are expected to reshape AD diagnostics. A stepwise approach, using plasma biomarkers as first-line tests followed by confirmatory CSF or PET, is currently the most feasible strategy. Ultimately, highly specific, brain-derived tau biomarkers may enable BBMs to replace CSF biomarkers.
L. Gaetani, Giovanna Nardi, Lucilla Parnetti· Expert Review of Neurotherap...· 0 citations
In cognitively unimpaired older adults, elevated blood p-tau217 was linked to faster shrinkage in AD-specific brain regions, whereas NfL and GFAP were associated with more widespread atrophy, with NfL also associated with accelerated WMH accumulation.
Martina Valletta, D. L. Vetrano, E. Laukka et al.· Annals of Neurology· 0 citations
Background and Objectives Sleep-wake dysregulation and elevated CSF orexin have been implicated in Alzheimer disease (AD). Sleep spindles (SPs) and slow oscillations (SOs) are linked to cognition and neurodegeneration; however, their relationship with CSF orexin concentrations in symptomatic AD has not been characterized. We investigated whether nonrapid eye movement (NREM) SP-SO activity is associated with CSF orexin and whether these oscillatory features moderate associations between orexin, cognition, neuropsychiatric symptom severity, and AD biomarkers. Methods This prospective observational cohort study was conducted at a tertiary memory clinic in Lleida, Spain. Individuals aged ≥60 years with biomarker-confirmed mild-to-moderate AD (National Institute on Aging-Alzheimer's Association criteria) underwent overnight polysomnography and morning CSF sampling. SP and SO were detected using validated automated algorithms with independent verification and visual quality control. CSF was assayed for orexin-A, amyloid-β42 (Aβ42), phosphorylated tau181 (pTau181), total tau, and YKL-40. Cognitive performance Alzheimer’s Disease Assessment Scale–Cognitive Subscale ([ADAS-Cog], Mini-Mental State Examination (MMSE), California verbal learning test, ROCF) and neuropsychiatric symptoms (NPI) were assessed longitudinally over 36 months. Associations were examined using generalized linear models with robust estimators adjusted for age, sex, Aβ42, and apnea-hypopnea index. Multiple comparisons were controlled using false discovery rate correction. Interaction terms assessed moderation effects. Results Sixty participants (30 women; mean age 74.7 years) were included. Longer SO duration and higher SP density and power were associated with lower CSF orexin concentrations (SP density: β = −187.37 pg/mL, 95% CI −344.93 to −29.80). Orexin was not associated with global sleep continuity metrics. Higher CSF orexin concentrations were associated with worse global cognition (ADAS-Cog: β = 0.014, 95% CI 0.003–0.024; MMSE: β = −0.01, 95% CI −0.011 to −0.004) and greater neuropsychiatric symptom severity (NPI at: β = 0.03, 95% CI 0.011–0.041). Higher orexin was also associated with higher pTau181 (β = 0.11, 95% CI 0.04–0.19), total tau, and YKL-40 (β = 0.37, 95% CI 0.17–0.57). Significant orexin × SP-SO interactions were observed, such that greater oscillatory activity attenuated the adverse associations between orexin and cognitive outcomes, independent of Aβ42 and tau. Discussion In biomarker-confirmed AD, NREM SP and SO activity are associated with CSF orexin concentrations and moderate associations between orexin and longitudinal cognitive and neuropsychiatric outcomes. Limitations include the observational design and absence of a comparator group, precluding causal inference and limiting contextualization relative to normal aging. NREM oscillatory metrics and orexin concentrations may represent complementary physiologic markers for disease monitoring and therapeutic targeting. Trial Registration Information Role of Hypoxia and Sleep Fragmentation in AD; ClinicalTrials.gov Identifier: NCT02814045.
Arsenio Páez, G. Piñol-Ripoll, A. Carnes-Vendrell et al.· Neurology· 0 citations