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BackgroundAs the prevalence of Alzheimer disease (AD) rises, early identification of at-risk individuals is essential for effective intervention. Mild behavioral impairment (MBI), which captures emergent and persistent neuropsychiatric symptoms (NPS) in later life, may enhance early detection of AD; however, its associations with 2024 NIA-AA Core 1 biomarkers remain unexplored. We investigated associations between MBI and cerebrospinal fluid (CSF) amyloid β-42 (Aβ42) and phosphorylated tau-181 (p-tau181).MethodBaseline data from 1327 dementia-free Alzheimer's Disease Neuroimaging Initiative (ADNI) participants were analyzed. Participants were classified as MBI, non-MBI NPS, or no NPS. Gaussian mixture modeling defined biomarker positivity. Logistic and multinomial logistic regressions modeled associations between NPS status and biomarker positivity or biomarker profiles, adjusting for age, sex, education, and cognition.ResultsMBI was associated with Aβ42+ (aOR = 2.26; 95% CI = 1.71-2.99), p-tau181+ (aOR = 1.72; 95% CI = 1.30-2.28), and AD continuum profile (aOR = 2.33; 95% CI = 1.73-3.14), but not with non-AD pathology. Non-MBI NPS showed no associations.ConclusionMBI may serve as a behavioral marker of AD pathology.
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http://dx.doi.org/10.1177/08919887251366634 | DOI Listing |
Proc Natl Acad Sci U S A
September 2025
School of Medicine, Chongqing University, Chongqing 400044, China.
Engineering functional exosomes represents a cutting-edge approach in biomedicine, holding the promise to transform targeted therapy. However, challenges such as achieving consistent modification and scalability have limited their wider adoption. Herein, we introduce a universal and effective strategy for engineering multifunctional exosomes through cell fusion.
View Article and Find Full Text PDFJAMA Netw Open
September 2025
School of Medicine and Public Health, University of Wisconsin-Madison, Madison.
Importance: It is unclear whether the duration of amyloid-β (Aβ) pathology is associated with neurodegeneration and whether this depends on the presence of tau.
Objective: To examine the association of longitudinal atrophy with Aβ positron emission tomography (PET)-positivity (Aβ+) and the estimated duration of Aβ+ (Aβ+ duration), controlling for tau-positivity.
Design, Setting, And Participants: Data for this longitudinal cohort study were drawn from the Wisconsin Registry for Alzheimer Prevention and the Wisconsin Alzheimer Disease Research Center Clinical Core Study.
Mol Biol Rep
September 2025
Department of Pharmacology, Govt. College of Pharmacy, Rohru, Shimla, Himachal Pradesh, 171207, India.
Alzheimer's disease (AD) is the most common, complex, and untreatable form of dementia which is characterized by severe cognitive, motor, neuropsychiatric, and behavioural impairments. These symptoms severely reduce the quality of life for patients and impose a significant burden on caregivers. The existing therapies offer only symptomatic relief without addressing the underlying silent pathological progression.
View Article and Find Full Text PDFNeurochem Res
September 2025
School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, 330004, China.
Metabolic synergy between astrocytes and neurons is key to maintaining normal brain function. As the main supporting cells in the brain, astrocytes work closely with neurons through intercellular metabolic synergy networks to jointly regulate energy metabolism, lipid metabolism, synaptic transmission, and cerebral blood flow. This important synergy is often disrupted in neurological diseases such as Alzheimer's disease, Parkinson's disease, and stroke.
View Article and Find Full Text PDFPsychopharmacology (Berl)
September 2025
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, 04510, Mexico.
Rationale: One of the earliest changes associated with Alzheimer's disease (AD) is the loss of catecholaminergic terminals in the cortex and hippocampus originating from the Locus Coeruleus (LC). This decline leads to reduced catecholaminergic neurotransmitters in the hippocampus, affecting synaptic plasticity and spatial memory. However, it is unclear whether restoring catecholaminergic transmission in the terminals from the LC may alleviate the spatial memory deficits associated with AD.
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