Related Experiment Video
Updated: Jun 27, 2026
10:32
Assessing Functional Performance in the Mdx Mouse Model
Published on: March 28, 2014
Functional border-associated macrophages limit Alzheimer's Disease progression
Drew Adler1,2,3, Natália Pinheiro-Rosa2, Alon Millet4,5
1Vilcek Institute of Graduate Biomedical Sciences, New York University Grossman School of Medicine; New York, NY, USA.
Biorxiv : the Preprint Server for Biology
|February 12, 2026
Summary
Border-associated macrophages (BAMs) are crucial in Alzheimer's Disease (AD) and cerebral amyloid angiopathy (CAA). Preserving BAM function offers a new therapeutic strategy for these neurodegenerative conditions.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Brain-resident macrophages, including microglia and border-associated macrophages (BAMs), are implicated in Alzheimer's Disease (AD) pathogenesis.
- Disentangling the specific roles of microglia versus BAMs in AD has been challenging.
- The gene Maf, identified through AD GWAS studies, is critical for BAM survival but not microglial survival.
Purpose of the Study:
- To investigate the contribution of BAMs to Alzheimer's Disease (AD) and cerebral amyloid angiopathy (CAA) progression.
- To explore the functional changes in BAMs during AD pathogenesis.
- To evaluate the therapeutic potential of preserving BAM function in AD.
Main Methods:
- Utilized BAM-depleted mice crossed with the 5xFAD AD model.
- Analyzed markers of cerebral amyloid angiopathy (CAA), beta-amyloid burden, and neurodegeneration.
- Assessed BAM and microglial endocytic capacity and metabolic state in AD models and human samples.
Main Results:
- BAM depletion in AD models exacerbated cerebral amyloid angiopathy (CAA), increased beta-amyloid load, and accelerated neurodegeneration and memory deficits.
- In healthy brains, BAMs exhibit higher beta-amyloid uptake than microglia.
- During AD progression, BAMs show reduced numbers, impaired endocytic function, and metabolic exhaustion earlier than microglia.
Conclusions:
- BAMs play a critical protective role in mitigating AD and CAA pathology.
- BAM dysfunction, characterized by reduced numbers and impaired phagocytic capacity, contributes significantly to AD progression.
- Strategies aimed at preserving or restoring BAM function represent a promising novel therapeutic avenue for Alzheimer's Disease and cerebral amyloid angiopathy.
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