Abstract. Forkhead box P3 (Foxp3) is a transcription factor that influences functioning of regulatory T cells (Tregs) that modulate peripheral immune respo

INTRODUCTION Obesity is a major modifiable risk factor for Alzheimer's disease (AD), but the mechanistic link between peripheral metabolic dysfunction and AD progression remains unclear. Adipose-der.....

Poor sleep health may accelerate brain ageing. This may be driven by higher levels of systemic inflammation.

Alzheimer’s disease (AD), marked by amyloid-beta (Aβ) plaques and tau tangles, involves cerebral amyloid angiopathy (CAA), which may compromise blood-brain barrier (BBB) integrity. However, the extent and nature of BBB disruption in AD remain unclear. This study assessed BBB permeability in Tg2576 AD mice by evaluating unidirectional paracellular transport from blood to brain following intravenous injection of the stable isotope-labeled marker [¹³C₁₂]sucrose. Pharmacokinetic analysis of plasma and brain concentrations 30 min post-injection revealed minimal sucrose passage across the BBB in both AD and wild-type (WT) mice, suggesting preserved BBB integrity despite Aβ deposition. Regional clearance rates in the hippocampus, cortex, and cerebellum were similar across groups, with only the olfactory bulbs showing increased uptake. Immunohistochemical analysis of BBB tight junction proteins (claudin-5, occludin, ZO-1) revealed no significant differences between AD and WT mice. High-resolution imaging showed minor tight junction disruptions near Aβ plaques, but laser microdissection and LC-MS/MS analysis revealed no increased sucrose concentrations in regions with vascular Aβ-deposition, indicating localized changes do not substantially affect BBB permeability. Our findings challenge the assumption of widespread BBB leakiness in the Tg2576 AD model, highlighting the need for multi-method approaches to assess BBB integrity and optimize drug delivery in AD.

How genetic predisposition drives late-onset disease risk remains unclear. Here, the authors show that epigenetic predisposition via NR3C1-dependent early postnatal 3D gene regulation primes astrocytes for lifelong immune vulnerability.

Some vaccine-preventable diseases are linked to accelerated brain atrophy and increased dementia risk years down the line.

The social exposome—lifelong social and economic adversity—can shape brain health and dementia risk. Here, the authors show that an adverse social exposome is linked to poorer clinical, cognitive, and...

ement of adaptive immunity, particularly T and B lymphocytes, in the neuroinflammatory processes of AD. It remains unclear how adaptive immune responses, originally intended to protect the body, contr...

Neurodegenerative diseases present one of the most significant global health challenges. These disorders are defined by the accumulation of abnorma...

We explored whether changes in serum proteomic profiles differed between participants with distinct brain aging trajectories, and whether these changes were influenced by dietary intervention.

INTRODUCTION Mutations in SORL1, encoding the sorting receptor Sortilin-related receptor with A-type repeats (SORLA), are found in individuals with Alzheimer's disease (AD). We studied SORLAN1358S, ...