Scientific reportsOct 14, 2024

Low to moderate alcohol exposure reduces brain support cell inflammation and memory decline in early-stage Alzheimer's mice

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Apr 3, 2026

Abstract

Moderate alcohol exposure reduced amyloid beta deposition in the brains of APP/PS1 mice.

Mice exposed to moderate ethanol showed reduced levels of astrocytic glial fibrillary acidic protein (GFAP) and (ApoE) in the cortex and hippocampus.
Increased expression of (LRP1) was observed, which may inhibit inflammatory pathways associated with neurodegeneration.
Levels of pro-inflammatory cytokines IL-1β and TNF-α decreased in male mice following moderate ethanol exposure.
Female mice exhibited reduced anti-inflammatory cytokines IL-4 and IL-10 without changes in IL-1β and TNF-α levels.
Aβ plaques were reduced in both sexes, suggesting a potential protective effect of moderate alcohol consumption against Alzheimer's disease.
Brain activity measured by FDG-PET increased, and cognitive deficits were normalized in both male and female APP/PS1 mice following moderate ethanol exposure.

Simplified

Alcohol use disorder has been associated with the development of neurodegenerative diseases, including Alzheimer's disease (AD). However, recent studies demonstrate that moderate alcohol consumption may be protective against dementia and cognitive decline. We examined astrocyte function, low-density lipoprotein (LDL) receptor-related protein 1 (), and the NF-κB p65 and IKK-α/β signaling pathways in modulating and amyloid beta (Aβ) deposition. We assessed (ApoE) in the brain of APP/PS1 mice using IHC and ELISA in response to low to moderate ethanol exposure (MEE). First, to confirm the intracerebral distribution of ApoE, we co-stained with GFAP, a marker for astrocytes that biosynthesize ApoE. We sought to investigate whether the ethanol-induced upregulation of LRP1 could potentially inhibit the activity of IL-1β and TNF-α induced IKK-α/β towards NF-κB p65, resulting in a reduction of pro-inflammatory cytokines. To evaluate the actual Aβ load in the brains of APP/PS1 mice, we performed with a specific antibody Aβ (Thioflavin S) on both air- and ethanol-exposed groups, subsequently analyzing Aβ levels. We also measured glucose uptake using 18F- fluorodeoxyglucose (FDG)-positron emission tomography (PET). Finally, we investigated whether MEE induced cognitive and memory changes using the Y maze, noble object recognition test, and Morris water maze. Our findings demonstrate that MEE reduced astrocytic glial fibrillary acidic protein (GFAP) and ApoE levels in the cortex and hippocampus in presymptomatic APP/PS1 mice. Interestingly, increased LRP1 protein expression was accompanied by dampening the IKK-α/β-NF-κB p65 pathway, resulting in decreased IL-1β and TNF-α levels in male mice. Notably, female mice show reduced levels of anti-inflammatory cytokines IL-4, and IL-10 without altering IL-1β and TNF-α concentrations. In both males and females, Aβ plaques, a hallmark of AD, were reduced in the cortex and hippocampus of APP/PS1 mice exposed to ethanol starting at pre-symptomatic stage. Consistently, MEE increased FDG-PET-based brain activities and normalized cognitive and memory deficits in the APP/PS1 mice. Our findings suggest that MEE may benefit AD pathology via modulating LRP1 expression, potentially reducing neuroinflammation and attenuating Aβ deposition. Our study implies that reduced astrocyte-derived ApoE and LDL cholesterol levels are critical for attenuating AD pathology.

Key numbers

notable reduction

Reduction in Aβ Plaques

Aβ plaque levels in cortex and hippocampus of ethanol-exposed presymptomatic APP/PS1 mice

170 mg/dl

Blood Alcohol Concentration

Average BAC in presymptomatic APP/PS1 mice after ethanol exposure

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Low to moderate alcohol exposure reduces brain support cell inflammation and memory decline in early-stage Alzheimer's mice

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