40 Hz Auditory + Visual Gamma Stimulation Reduces Amyloid and Entrains LFP in 5xFAD Mice

In_Vivo Score: 0.772 Price: $0.50 Alzheimer's disease 5xFAD mice 4-6 months, LFP implant (hippocampus CA1), n=10/group x 4 groups Status: proposed

What This Experiment Tests

In_Vivo experiment designed to assess clinical efficacy targeting N/A in 5xFAD mice 4-6 months, LFP implant (hippocampus CA1), n=10/group x 4 groups. Primary outcome: Hippocampal soluble Abeta42 reduced >=40% vs sham; CA1 LFP 40 Hz power >=2x baseline

Description

Determine whether combined 40 Hz auditory (click train) + visual (flickering LEDs) gamma entrainment, 1 h/day x 4 weeks, reduces soluble Abeta and tau in hippocampus and entrains LFP gamma power >=2-fold above baseline in 5xFAD mice.

TARGET GENE

N/A

MODEL SYSTEM

5xFAD mice 4-6 months, LFP implant (hippocampus CA1), n=10/group x 4 groups

ESTIMATED COST

$72,000

TIMELINE

14 months

PATHWAY

40 Hz oscillation -> glymphatic activation -> microglial Abeta clearance

SOURCE

task:a989715e-c687-4558-91ca-74fce1474bd2

PRIMARY OUTCOME

Hippocampal soluble Abeta42 reduced >=40% vs sham; CA1 LFP 40 Hz power >=2x baseline

Scoring Dimensions

Protocol

Implant tetrode LFP arrays in CA1 of 5xFAD and WT mice at 4 months. 2. Recovery 1 week; then 4 treatment groups: WT-sham, 5xFAD-sham, 5xFAD-visual-only, 5xFAD-combined. 3. Stimulation: 1 h/day, 5 days/week, 4 weeks (20 sessions). 4. Weekly: open field, NOR. 5. Post-treatment: - Ex vivo LFP power spectral analysis (gamma 30-80 Hz) - ELISA: soluble Abeta40, Abeta42 (hippocampus) - IHC: Iba1 microglia morphology, 6E10 plaque burden, AQP4 (glymphatic) 6. Primary: soluble Abeta42 ELISA; secondary: LFP gamma power, NOR, plaque count.

Expected Outcomes

Combined stimulation will entrain CA1 gamma >=2x baseline, reduce soluble Abeta42 >=40%, activate microglia phagocytosis, and improve NOR discrimination index.

Success Criteria

Primary: Abeta42 ELISA >=40% reduction vs 5xFAD-sham (Student t, p<0.05). Secondary: LFP 40 Hz power >=2x baseline during stimulation; NOR DI >=0.65.

Related Hypotheses (1)

Gamma Oscillation Enhancement Synergy0.838

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