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Basic Science and Pathogenesis.

Methasit Jaisa-Aad1,2,3, Cinthya Aguero1,2,3, Neus Rabaneda-Lombarte1,2,3

  • 1MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
PubMed
Summary
This summary is machine-generated.

Monoamine oxidase-B (MAO-B) is upregulated in reactive astrocytes in Alzheimer's disease (AD) and related dementias (ADRD). MAO-B may identify neurotoxic astrocytes and serve as a PET imaging target for predicting neurodegeneration.

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Area of Science:

  • Neuroscience
  • Neuropathology
  • Molecular Biology

Background:

  • Reactive astrogliosis is complex in Alzheimer's disease (AD) and AD-related dementias (ADRD).
  • Previous single nucleus RNA-sequencing identified astrocyte heterogeneity and markers in AD.
  • Monoamine oxidase-B (MAO-B) is implicated in oxidative stress and GABAergic inhibition, with potential as a PET imaging biomarker for reactive astrogliosis.

Purpose of the Study:

  • To evaluate monoamine oxidase-B (MAO-B) as a marker of reactive astrocytes in AD and ADRD.
  • To investigate the association between MAO-B expression and neurodegeneration markers.

Main Methods:

  • Quantitative immunohistochemistry for MAO-B, GFAP, YKL-40, Aβ, pTau, and pTDP43 in human brain tissue from controls and patients with AD, Pick's disease, PSP, CBD, and FTLD-TDP.
  • Confocal and super-resolution microscopy to assess MAO-B expression and localization in astrocytes.
  • Measurement of cortical thickness as a proxy for atrophy.

Main Results:

  • MAO-B immunoreactivity was significantly increased in the frontal cortex and white matter in AD, CBD, Pick's disease, and FTLD-TDP compared to controls.
  • MAO-B area fraction positively correlated with GFAP and YKL-40.
  • MAO-B was primarily expressed by cortical astrocytes and localized to mitochondria; it was negatively associated with cortical thickness, independent of Aβ, pTau, or pTDP43.

Conclusions:

  • MAO-B upregulation may identify a subset of neurotoxic reactive astrocytes in AD/ADRD.
  • MAO-B radioligand binding could potentially predict future neurodegeneration in AD/ADRD, warranting further PET-MRI studies.