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Drug Development.

Xiaoyi Yang1, Zhuowei Gong2, Fangzheng Tian2

  • 1NYU Grossman School of Medicine, New York, NY, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

The synthetic peptide Aβ12-28P significantly reduced anxiety in middle-aged and old Alzheimer's disease (AD) mice. This peptide targets amyloid-beta (Aβ) pathology, offering a potential strategy for treating anxiety in AD patients.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Gerontology

Background:

  • Anxiety is a common neuropsychiatric symptom in Alzheimer's disease (AD).
  • Anxiety in AD is linked to amyloid-beta (Aβ) plaques and neurofibrillary tangles.
  • Previous studies showed Aβ12-28P improved cognition in aged AD mice.

Purpose of the Study:

  • To investigate the anxiolytic effects of Aβ12-28P in AD mouse models.
  • To explore the impact of Aβ12-28P on anxiety-related neural activity in AD mice.

Main Methods:

  • APP/PS1 dE9 mice (middle-aged and old) received Aβ12-28P or saline injections.
  • Behavioral tests (open field, elevated plus maze) assessed anxiety levels.
  • In vivo fiber photometry recorded neural dynamics in key brain regions (vCA1, mPFC, BA, LHA).

Main Results:

  • Aβ12-28P demonstrated acute anxiolytic effects in both middle-aged and old AD mice.
  • Significant anxiety reduction was observed in the open field and elevated plus maze tests.
  • Fiber photometry revealed Aβ12-28P modified anxiety-associated neural dynamics in targeted brain regions.

Conclusions:

  • Aβ12-28P exhibits acute anxiolytic properties in AD mouse models.
  • Targeting Aβ pathology with Aβ12-28P is a promising strategy for alleviating anxiety in AD.
  • The study provides insights into brain region-specific mechanisms of this therapeutic approach.