Importance: Anemia has been associated with increased dementia risk, but its relationship with Alzheimer disease (AD) blood biomarkers remains unclear. Objective: To investigate whether there is a cross-sectional association between hemoglobin and AD blood biomarker levels and a longitudinal association of hemoglobin and AD biomarkers with incident dementia. Design, Setting, and Participants: This cohort study used data from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a longitudinal population-based study. Randomly selected adults aged 60 years or older were enrolled at baseline (March 21, 2001, to August 30, 2004) and followed up every 3 or 6 years according to age through December 31, 2019. Data analysis was conducted between September 1, 2024, and January 7, 2026. Exposures: Hemoglobin level measured at baseline. Anemia was defined according to World Health Organization criteria. Main Outcomes and Measures: Incident dementia, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and serum concentrations of phosphorylated tau 217 (p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP), measured using Simoa assays. Cox proportional hazards regression and quantile regression models were used to examine the association of hemoglobin with dementia risk and AD blood biomarkers. The joint association of hemoglobin and AD blood biomarkers with dementia development using Cox proportional hazards regression was also explored. Results: A total of 3363 adults were enrolled in SNAC-K (73.3% participation rate). After excluding those with dementia or missing AD biomarkers or hemoglobin measures, 2282 dementia-free participants were included in the current study (median age, 72.2 [IQR, 60.8-81.1] years; 1406 [61.6%] female). During a mean (SD) follow-up of 9.3 (4.3) years, 362 participants (15.9%) developed dementia. Compared with individuals with a normal hemoglobin level, those with anemia had higher baseline levels of p-tau217 (β, 0.22; 95% CI, 0.15-0.30), NfL (β, 0.25; 95% CI, 0.19-0.31), and GFAP (β, 0.08; 95% CI, 0.03-0.12) and showed a higher risk of developing dementia (hazard ratio [HR], 1.66; 95% CI, 1.21-2.28) during follow-up. Participants with both anemia and high p-tau217, NfL, or GFAP had the highest hazard of dementia (eg, adjusted HR of 3.64 [95% CI, 2.39-5.56] among those with anemia and high NfL). Conclusions and Relevance: In this cohort study of dementia-free older adults, anemia was associated cross-sectionally with higher levels of AD blood biomarkers and longitudinally with increased dementia risk. The highest dementia risk occurred when low hemoglobin and elevated AD biomarkers coexisted, suggesting a potential interplay between anemia and neuropathology in dementia development.

Background Age-related muscle function decline is a major impediment to healthy ageing. We aimed to investigate the association between a panel of Alzheimer's disease-related biomarkers and longitudinal trajectories of muscle strength, while exploring the influence of cognitive function. Methods In this cohort study, we gathered data from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K), an ongoing prospective study that includes adults aged 60 years and older, from central Stockholm, Sweden. We included data from baseline to the fourth follow-up (March 21, 2001, to Dec 31, 2016). Seven Alzheimer's disease-related blood biomarkers were measured in dementia-free, community dwelling participants: total tau, phosphorylated tau181 (p-tau181), phosphorylated tau217 (p-tau217), amyloid beta 40 and 42, neurofilament light chain, and glial fibrillary acidic protein (GFAP). Muscle strength was measured through the handgrip strength and chair-stand tests. Linear mixed models were used to explore the association between baseline Alzheimer's disease-related biomarkers and muscle strength trajectories. Findings The baseline SNAC-K cohort included 3363 individuals, of whom 1953 participants were included in our analyses (mean age 70.2 [SD 9.1] years; 780 [39.9%] male and 1173 [60.1%] female participants). In adjusted models, higher concentrations of p-tau181 (beta per year 0.93 [95% CI 0.71 to 1.16]; p<0.0001), p-tau217 (beta per year 1.31 [1.03 to 1.58]; p<0.0001), neurofilament light chain (beta per year 0.76 [0.56 to 0.96]; p<0.0001), and GFAP (beta per year 0.37 [0.21 to 0.53]; p<0.0001) were associated with an accelerated decline of chair-stand performance over time. The adjustment for Mini-Mental State Examination (MMSE) score led to the attenuation of these associations. Higher concentrations of p-tau181 (beta per year-0.12 [95% CI-0.17 to-0.07]; p<0.0001), p-tau217 (beta per year-0.13 [-0.20 to-0.07]; p<0.0001), and neurofilament light chain (beta per year-0.05 [-0.09 to-0.001]; p=0.047) were also associated with faster handgrip strength decline, with no attenuation after adjusting for MMSE score. Sex-specific differences were observed, with female participants showing a stronger association between biomarker concentrations and muscle strength decline than male participants, particularly in the chair-stand test. Interpretation Our findings suggest that blood Alzheimer's disease-related biomarkers might help estimate progressive muscle strength decline among older adults, elucidating the influence of brain pathology and cognitive ageing on this association. These Alzheimer's disease-related biomarkers could aid in identifying individuals for early intervention to prevent sarcopenia. Copyright

Blood biomarkers of Alzheimer’s disease (AD) are promising for dementia prediction, but their association with progression across intermediate stages of cognitive decline in the general population remains unclear. We followed 2148 dementia-free individuals from a Swedish population-based cohort for up to 16 years. Associations between baseline AD blood biomarkers and transitions between normal cognition, mild cognitive impairment (MCI), and dementia were examined. Lower amyloid-β42/40 ratio and higher phosphorylated-tau181 (p-tau181), p-tau217, total-tau, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were associated with faster progression from MCI to all-cause and AD dementia, with the strongest associations for NfL and p-tau217. Elevated NfL and GFAP were linked to reduced MCI reversion to normal cognition, whereas no biomarker was associated with MCI development from normal cognition. These findings show robust group-level associations and indicate that AD blood biomarkers may help stratify dementia risk at the MCI stage in the community.

Evidence regarding the clinical validity of blood biomarkers of Alzheimer's disease (AD) in the general population is limited. We estimated the hazard and predictive performance of six AD blood biomarkers for incident all-cause and AD dementia-the ratio of amyloid-beta 42 to amyloid-beta 40 and levels of tau phosphorylated at T217 (p-tau217), tau phosphorylated at T181 (p-tau181), total tau, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP)-in a cohort of 2,148 dementia-free older adults from Sweden, who were followed for up to 16 years. In multi-adjusted Cox regression models, elevated baseline levels of p-tau181, p-tau217, NfL, and GFAP were associated with a significantly increased hazard for all-cause and AD dementia, displaying a non-linear dose-response relationship. Elevated concentrations of p-tau181, p-tau217, NfL, and GFAP demonstrated strong predictive performance (area under the curve ranging from 70.9% to 82.6%) for 10-year all-cause and AD dementia, with negative predictive values exceeding 90% but low positive predictive values (PPVs). Combining p-tau217 with NfL or GFAP further improved prediction, with PPVs reaching 43%. Our findings suggest that these biomarkers have the potential to rule out impending dementia in community settings, but they might need to be combined with other biological or clinical markers to be used as screening tools.

INTRODUCTION: We explored the variations of blood biomarkers of Alzheimer's disease (AD) by chronic diseases and systemic inflammation.

METHODS: We explored the association of AD blood biomarkers with chronic diseases and systemic inflammation (interleukin‐6 [IL‐6]), in 2366 dementia‐free participants of the Swedish National Study on Aging and Care‐in Kungsholmen, using quantile regression models.

RESULTS: A greater number of co‐occurring chronic diseases was associated with higher concentrations of phosphorylated‐tau 181 (p‐tau181), total‐tau (t‐tau), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) ( p  < 0.01). Anemia, kidney, cerebrovascular, and heart diseases were associated with variations in the levels of AD blood biomarkers. Participants in the highest (vs. lowest) interleukin‐6 (IL‐6) tertile had higher NfL concentration. Systemic inflammation amplified the associations between several chronic diseases and p‐tau181, t‐tau, NfL, and GFAP.

DISCUSSION: In the community, the concentration of AD blood biomarkers varies in relation to medical conditions and systemic inflammation. Recognizing these influences is crucial for the accurate interpretation and clinical implementation of blood biomarkers.

Highlights: Participants with a complex clinical profile (i.e., multiple co‐occurring diseases or specific disease combinations) display elevated levels of AD blood‐biomarkers. Anemia, heart, cerebrovascular, and kidney diseases are associated with variations is the levels of AD blood biomarkers in cognitively intact older adults. Systemic inflammation amplifies the association between several chronic diseases and AD blood biomarkers. Participants with a complex clinical profile (i.e., multiple co‐occurring diseases or specific disease combinations) display elevated levels of AD blood‐biomarkers.Anemia, heart, cerebrovascular, and kidney diseases are associated with variations is the levels of AD blood biomarkers in cognitively intact older adults.Systemic inflammation amplifies the association between several chronic diseases and AD blood biomarkers.

Membrane proteins on enveloped viruses play an important role in many biological functions involving virus attachment to target cell receptors, fusion of viral particles to host cells, host-virus interactions, and disease pathogenesis. Furthermore, viral membrane proteins on virus particles and presented on host cell surfaces have proven to be excellent targets for antivirals and vaccines. Here, we describe a protocol to investigate surface proteins on intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) particles using the dual-reporter flow cytometric system. The assay exploits multiplex technology to obtain a triple detection of viral particles by three independent affinity reactions. Magnetic beads conjugated to recombinant human angiotensin-converting enzyme-2 (ACE2) were used to capture viral particles from the supernatant of cells infected with SARS-CoV-2. Then, two detection reagents labeled with R-phycoerythrin (PE) or Brilliant Violet 421 (BV421) were applied simultaneously. As a proof-of-concept, antibody fragments targeting different epitopes of the SARS CoV-2 surface protein Spike (S1) were used. The detection of viral particles by three independent affinity reactions provides strong specificity and confirms the capture of intact virus particles. Dose-dependency curves of SARS-CoV-2 infected cell supernatant were generated with replicate coefficient variances (mean/SD) ˂14%. Good assay performance in both channels confirmed that two virus surface target protein epitopes are detectable in parallel. The protocol described here could be applied for (i) high-multiplex, high-throughput profiling of surface proteins expressed on enveloped viruses; ii) detection of active intact viral particles; and (iii) assessment of specificity and affinity of antibodies and antiviral drugs for surface epitopes of viral antigens.The application can be potentially extended to any type of extracellular vesicles and bioparticles, exposing surface antigens in body fluids or other liquid matrices.