Biomarkers

Area of Science:

• Neuroscience
• Pharmacology
• Clinical Medicine

Background:

• Hippocampal hyperactivity is a key feature of Alzheimer's disease (AD) and mild cognitive impairment (MCI).
• This overactivity, stemming from an imbalance in neural activity, drives neurodegeneration and tau pathology spread.
• AGB101, a low-dose levetiracetam formulation, aims to normalize hippocampal activity and improve cognition in MCI patients.

Purpose of the Study:

• To assess the efficacy of AGB101 in slowing progression in amyloid-positive MCI patients.
• To evaluate the impact of AGB101 on cognitive decline and neurodegeneration over 78 weeks.

Main Methods:

• 164 amyloid-positive MCI participants were randomized to AGB101 or placebo.
• The primary outcome measure was the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB).
• MRI and plasma biomarker analyses were conducted at baseline and 78 weeks.

Main Results:

• In ApoE-4 non-carriers, AGB101 showed a 40% benefit on CDR-SB versus placebo.
• AGB101 significantly reduced entorhinal cortex atrophy in ApoE-4 non-carriers.
• This reduction in atrophy correlated with CDR-SB changes and plasma biomarkers (NFL, GFAP).

Conclusions:

• Low-dose levetiracetam (AGB101) normalizes aberrant brain network activity.
• AGB101 demonstrated meaningful benefit and reduced neurodegeneration in ApoE-4 non-carriers with MCI due to AD.
• Further investigation of AGB101 in this specific patient group is recommended.