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Introduction: Late-life mood disorders (LLMDs) may represent prodromal manifestations of neurodegenerative dementia; however, the neuropathological basis of LLMDs, including depression and bipolar disorder, remains unclear. We aimed to investigate the involvement of Alzheimer's disease (AD) and non-AD tau pathologies in LLMD participants.
Methods: Fifty-two LLMD participants and 47 age- and sex-matched healthy controls (HCs) underwent tau and amyloid beta (Aβ) positron emission tomography (PET) imaging using F-florzolotau and C-Pittsburgh compound B. Additionally, we conducted a clinicopathological correlation analysis in 208 autopsy cases, including various neurodegenerative diseases.
Results: LLMD participants were more likely to be tau PET and Aβ PET positive than HCs. The PET results were supported by the post mortem results that showed a higher likelihood of diverse tauopathies in patients with late-life mania or depression than those without.
Discussion: Our PET and autopsy assays suggest that AD and diverse non-AD tau pathologies might underlie the neuropathological basis of some LLMD cases.
Highlights: Late-life mood disorders (LLMDs) may represent prodromal states of dementia. The neuropathological basis of LLMDs remains unclear. LLMD subjects were highly likely to be tau positron emission tomography (PET) positive. Brain bank data supported our PET results. Alzheimer's disease (AD) and diverse non-AD tau pathologies can contribute to LLMDs.
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http://dx.doi.org/10.1002/alz.70195 | DOI Listing |
Biomed Pharmacother
September 2025
Department of Pharmacology, College of Dentistry, Jeonbuk National University, Jeonju 54896, Republic of Korea. Electronic address:
Alzheimer's disease (AD) is marked by amyloid-beta (Aβ) plaque buildup, tau hyperphosphorylation, neuroinflammation, neuronal loss, and impaired adult hippocampal neurogenesis (AHN). Taurine has shown protective effects in various cellular and animal models of AD, though the molecular mechanisms of free taurine and its effects in patient-derived models remain underexplored. This study evaluates taurine's therapeutic potential using integrated in silico, in vitro, in vivo, and ex vivo approaches.
View Article and Find Full Text PDFFASEB J
September 2025
Institute of Anatomy and Histology & Embryology, Neuroscience, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, People's Republic of China.
Alzheimer's disease (AD) is influenced by genetic and environmental factors. Previous studies showed that enriched environments improved memory and reduced amyloid plaques in AD mice, but the underlying mechanisms remain unclear. This study investigated the effects and mechanisms of enriched environments on AD pathology and cognitive function in aged APP/PS1 mice.
View Article and Find Full Text PDFNat Commun
September 2025
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
The distribution of tau pathology in Alzheimer's disease (AD) shows remarkable inter-individual heterogeneity, including hemispheric asymmetry. However, the factors driving this asymmetry remain poorly understood. Here we explore whether tau asymmetry is linked to i) reduced inter-hemispheric brain connectivity (potentially restricting tau spread), or ii) asymmetry in amyloid-beta (Aβ) distribution (indicating greater hemisphere-specific vulnerability to AD pathology).
View Article and Find Full Text PDFAlzheimers Dement
September 2025
Department of Clinical and Health Psychology, University of Florida, Gainesville, Florida, USA.
Introduction: Glial fibrillary acidic protein (GFAP) may contribute to Alzheimer's pathology at early disease stages. GFAP moderation of Alzheimer's disease (AD)-related neurodegeneration and cognition is unclear.
Methods: We examined plasma GFAP moderation of AD biomarkers (amyloid beta [Aβ]-positron emission tomography [PET][A]; plasma phosphorylated tau-181 [p-tau181][T]), neurodegeneration (plasma NfL[N]; structural magnetic resonance imaging [MRI][N]), and cognition (Cog; Cog) in two cohorts: University of California San Francisco (UCSF) (N = 212, 91.
JAMA Netw Open
September 2025
Department of Neurosciences, University of California, San Diego, La Jolla.
Importance: Subjective cognitive decline (SCD) may be an early indicator of Alzheimer disease and related dementias (ADRD), yet its association with plasma biomarkers remains unclear among middle-aged and older adults (aged 50-86 years).
Objective: To examine associations between plasma biomarkers of amyloid, tau, neuroaxonal damage, and glial activation with SCD in a heterogeneous cohort of Hispanic and/or Latino adults.
Design, Setting, And Participants: This cross-sectional study used survey-weighted data from the Study of Latinos-Investigation of Neurocognitive Aging, an ancillary study of the Hispanic Community Health Study/Study of Latinos.