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Background: The NIA-AA Research Framework on Alzheimer's disease (AD) proposes a transitional stage (stage 2) characterized by subtle cognitive decline, subjective cognitive decline (SCD) and mild neurobehavioral symptoms (NPS).
Objective: To identify participant clusters based on stage 2 features and assess their association with amyloid positivity in cognitively unimpaired individuals.
Methods: We included baseline data of N = 338 cognitively unimpaired participants from the DELCODE cohort with data on cerebrospinal fluid biomarkers for AD. Classification into the AD continuum (i.e., amyloid positivity, A+) was based on Aβ42/40 status. Neuropsychological test data were used to assess subtle objective cognitive dysfunction (OBJ), the subjective cognitive decline interview (SCD-I) was used to detect SCD, and the Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess NPS. A two-step cluster analysis was carried out and differences in AD biomarkers between clusters were analyzed.
Results: We identified three distinct participant clusters based on presented symptoms. The highest rate of A+ participants (47.6%) was found in a cluster characterized by both OBJ and SCD. A cluster of participants that presented with SCD and NPS (A+:26.6%) and a cluster of participants with overall few symptoms (A+:19.7%) showed amyloid positivity in a range that was not higher than the expected A+ rate for the age group. Across the full sample, participants with a combination of SCD and OBJ in the memory domain showed a lower Aβ42/ptau181 ratio compared to those with neither SCD nor OBJ.
Conclusions: The cluster characterized by participants with OBJ and concomitant SCD was enriched for amyloid pathology.
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http://dx.doi.org/10.3233/JAD-231335 | DOI Listing |
Neuropathol Appl Neurobiol
October 2025
Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Târgu Mureș, Romania.
Aims: The clusterin (CLU) gene is genetically associated with Alzheimer's disease (AD), and CLU levels have been shown to positively correlate with regional Aβ deposition in the brain, including in arteries from cerebral amyloid angiopathy (CAA) patients. CLU has also been shown to alter the aggregation, toxicity and blood-brain barrier transport of amyloid beta (Aβ) and has therefore been suggested to play a key role in regulating the balance between Aβ deposition and clearance in both the brain and cerebral blood vessels. However, it remains unclear whether the role of clusterin in relation to Aβ deposition is protective or pathogenic.
View Article and Find Full Text PDFSleep Adv
July 2025
Waisman Center, University of Wisconsin, Madison, Madison, WI 53705, United States.
This study provided a preliminary examination of indices of obstructive sleep apsnea (OSA) and sleep disruptions in adults with Down syndrome (DS), and their associations with Alzheimer's disease (AD) pathology and symptomatology. A total of 93 adults with DS (aged 25-61 years) from the Alzheimer Biomarker Consortium-DS completed cognitive assessments, MRI and positron emission tomography (PET) scans (assessing amyloid-beta [Aβ] and tau), and a one-night home sleep study using the WatchPAT-300 device. Study partners also reported on depressive symptoms and diagnoses.
View Article and Find Full Text PDFNPJ Dement
September 2025
C2N Diagnostics, LLC, St. Louis, MO USA.
The diagnostic performance of the Amyloid Probability Score 2 (APS2; the algorithmic result of the PrecivityAD2™ blood test) was originally trained and validated in two cohorts of cognitively impaired (CI) individuals and is in clinical use. Here, we further test the repeatability and reliability of the prespecified APS2 algorithm and cut point in an independent cohort. APS2 diagnostic performance was determined using amyloid positron emission tomography (PET) as the reference standard.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
Environmental Science and Engineering, Tianjin University, Tianjin, 300350, PR China.
Stable, treatment-resistant Cu complexes in practical wastewater are frequently neglected. Positively charged lysozyme amyloid fibrils (AF), however, exhibit unexplored potential for their adsorption. This study engineered an amyloid fibril-chitosan composite (AF-CS) xerogel and evaluated its adsorption performance in three systems: free Cu, Cu-Citrate binary, and Cu-EDTA binary.
View Article and Find Full Text PDFGeroscience
September 2025
Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Kangwon, 24341, Republic of Korea.
Alzheimer's disease (AD) represents a growing global health burden, underscoring the urgent need for reliable diagnostic and prognostic biomarkers. Although several disease-modifying treatments have recently become available, their effects remain limited, as they primarily delay rather than halt disease progression. Thus, the early and accurate identification of individuals at elevated risk for conversion to AD dementia is crucial to maximize the effectiveness of these therapies and to facilitate timely intervention strategies.
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