Hematopoietic stem cell transplant is the gold standard for treatment of globoid cell leukodystrophy, also called Krabbe disease. Aisenberg et al. define the molecular signature of disease-associated macrophages (globoid cells) and demonstrate that brain-specific high-efficiency macrophage replacement in the twitcher model of Krabbe disease improves neuropathology, macrophage dysfunction, and survival.

The niche signals critical for the homeostasis and functions of the brain border-associated macrophages (BAMs) are not well understood. Van Hove et al. demonstrate that BAMs require IL-34 derived from mural cells and perivascular fibroblasts for their maintenance in adulthood. They show that BAMs are required to promote normal vascular function in the brain.

Replacing brain macrophages holds substantial therapeutic promise but remains challenging. Bastos et al. uncover the requirements for monocytes to replace microglia and border-associated macrophages. They show that monocyte ontogeny shapes brain macrophage identity, with fetal monocytes acquiring a true microglial state. Using xenotransplantation and Alzheimer’s patient data, they identify human monocyte-derived microglia. These findings are important for microglia replacement therapies.

Murphy et al. develop CHAS, a computational tool that uncovers cell type-specific patterns in bulk tissue histone acetylation data. Applying CHAS to brain disorders reveals distinct cell type targets ...

Alzheimer’s Disease Strategic Fund: Vascular Contributions to Cognitive Impairment and Dementia - Understanding Mechanisms of Dysfunction (VCID-UMD) – learn about grant objectives, eligibility and dea...

Widespread delivery of therapeutic proteins to the brain remains challenging. To determine whether human induced pluripotent stem cell (iPSC)-microgli…

Parkinson's researcher Malú Tansey brings cell-level science to IU’s already strong clinical research program. Her lab engages in "paradigm-shifting work" studying inflammation and immune...

The immune-checkpoint molecule TIM-3 regulates microglial homeostasis, and its microglial-specific deletion reduced cognitive impairment in a mouse model of Alzheimer’s disease.

The ratio between the levels of two synaptic proteins in cerebrospinal fluid predicts future cognitive resilience versus decline among presymptomatic individuals and individuals with early Alzheimer’s...

Disruption of mucin-domain glycoprotein expression and function in the endothelial glycocalyx are associated with ageing and Alzheimer’s disease, leading to dysregulated blood–brain barrier function.

A naturally occurring missense variant of the phospholipase C isozyme, PLC-γ2, harboring a single substitution (P522R) protects against several neurodegenerative diseases, including Alzheimer’s diseas...