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Updated: Jun 27, 2026

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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
PubMed

Insights

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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