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Isotope-encoded spatial biology identifies plaque-age-dependent maturation and synaptic loss in an Alzheimer's disease mouse model

2 months 3 weeks ago
Understanding how amyloid beta (Aβ) plaques develop and lead to neurotoxicity in Alzheimer's disease remains a major challenge, particularly given the temporal delay and weak correlation between plaque deposition and cognitive decline. This study investigates how the evolving pathology of plaques affects the surrounding tissue, using a knock-in Aβ mouse model (App^(NL-F/NL-F)). We combined mass spectrometry imaging with stable isotope labeling to timestamp Aβ plaques from the moment of their...
Jack I Wood

Prioritising the primary prevention of heart failure

2 months 3 weeks ago
Heart failure remains one of the 21st century's greatest unmet clinical and public health challenges. Heart failure is a highly prevalent chronic condition that affects approximately 55 million people worldwide. Although heart failure can be prevented, the global burden of this condition continues to grow, fuelled by an ageing population, improved survival after myocardial infarction, and increasing prevalence of metabolic and kidney disease. Public health efforts for cardiovascular disease...
Sadiya S Khan

Isotope-encoded spatial biology identifies plaque-age-dependent maturation and synaptic loss in an Alzheimer's disease mouse model

2 months 3 weeks ago
Understanding how amyloid beta (Aβ) plaques develop and lead to neurotoxicity in Alzheimer's disease remains a major challenge, particularly given the temporal delay and weak correlation between plaque deposition and cognitive decline. This study investigates how the evolving pathology of plaques affects the surrounding tissue, using a knock-in Aβ mouse model (App^(NL-F/NL-F)). We combined mass spectrometry imaging with stable isotope labeling to timestamp Aβ plaques from the moment of their...
Jack I Wood

Global epidemiology and burden of osteoporosis among postmenopausal women: insights from the Global Burden of Disease Study 2021

2 months 3 weeks ago
Osteoporosis, primarily characterized by low bone mineral density (LBMD), is a major skeletal disorder among postmenopausal women (PMW), yet its global burden remains poorly quantified. Leveraging data from the Global Burden of Disease (GBD) Study 2021, we assessed the LBMD burden in PMW across 204 countries and territories between 1990 and 2021. Metrics included deaths, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs), with temporal...
Haofeng Liang

REV-ERBα regulates brain NAD<sup>+</sup> levels and tauopathy via an NFIL3-CD38 axis

2 months 3 weeks ago
Nicotinamide adenine dinucleotide (NAD^(+)) is a critical metabolic co-enzyme implicated in brain aging, and augmenting NAD^(+) levels in the aging brain is an attractive therapeutic strategy for neurodegeneration. However, the molecular mechanisms of brain NAD^(+) regulation are incompletely understood. In cardiac tissue, the circadian nuclear receptor REV-ERBα has been shown to regulate NAD^(+) via control of the NAD^(+)-producing enzyme NAMPT. Here we show that REV-ERBα controls brain NAD^(+)...
Jiyeon Lee

Failure of efficient cardiac proteostatic adaptations to chronic cAMP-stress is associated with accelerated heart aging

2 months 3 weeks ago
Dysregulated proteostasis is a hallmark of aging. We investigated how efficiently proteostatic adaptations to chronic cardiac cyclic-adenosine-monophosphate (cAMP)-dependent stress change with aging in mice harboring marked cardiac-specific over-expression of adenylyl cyclase VIII (TG^(AC8)). We assessed protein quality control mechanisms (PQC) (ubiquitin proteasome system, autophagic flux via macroautophagy, and mitophagy) in left ventricles of TG^(AC8) and wild-type littermates (WT) at 3-4 and...
Maria Grazia Perino

Normal Ageing Impacts the Extent and Diversity of Neural Plasticity Induced in the Mouse Brain With Repetitive Transcranial Magnetic Stimulation

2 months 3 weeks ago
Repetitive transcranial magnetic stimulation (rTMS) is an attractive tool to promote healthy brain ageing in older adults and treat age-related neurological conditions. Despite its popularity, the neurological processes and plasticity mechanisms altered by rTMS in the aged brain, and where these changes occur in the brain are unknown. Furthermore, it is not known why different rTMS protocols induce different changes in the aged brain, or why rTMS is less effective in older adults compared to...
Rebecca C S Ong