Alcohol Consumption and Alzheimer's Disease Pathology

Alcohol consumption exerts a complex influence on the development and progression of Alzheimer’s disease (AD), with evidence indicating that both dosage and pattern of intake modulate neuropathological outcomes. Heavy or binge drinking has been consistently associated with acceleration of core AD hallmarks, including amyloid-β (Aβ) accumulation, tau hyperphosphorylation and a sustained proinflammatory milieu within the brain. Conversely, low to moderate ethanol intake may engage neuroprotective pathways, though these observations remain contentious due to methodological variability across studies. Mechanistically, alcohol can alter cerebral Aβ synthesis and clearance by modulating key enzymes and receptors, perturb glial function by inducing astrocytic and microglial activation, disrupt autophagy and lysosomal degradation of pathological proteins, and promote oxidative stress and blood–brain barrier dysfunction. In parallel, liver injury induced by chronic alcohol intake may reshape peripheral-to-central Aβ homeostasis, linking hepatic steatosis with cerebral amyloidosis. Sex and age also influence vulnerability, with female animals often exhibiting more pronounced tau and Aβ changes following ethanol exposure. Understanding these interwoven pathways has far-reaching implications for public health, as alcohol use remains widespread and potentially modifiable, offering opportunities for risk reduction through behavioural and pharmacological interventions.

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Alcohol Consumption and Alzheimer's Disease Pathology publication trend

The graph below shows the total number of articles in alcohol consumption and alzheimer's disease pathology across all publications each year (not limited to Nature Index journals).

Technical terms

Amyloid precursor protein (APP): A transmembrane protein cleaved by secretases to produce amyloid-β peptides implicated in plaque formation.

Amyloid-β (Aβ): Peptides derived from APP whose aggregation into oligomers and plaques is a central feature of Alzheimer’s pathology.

Tau hyperphosphorylation: Excessive addition of phosphate groups to tau protein, promoting neurofibrillary tangle formation and neuronal dysfunction.

Neuroinflammation: Activation of glial cells and release of proinflammatory cytokines within the central nervous system contributing to neurodegeneration.

Astrocytic amyloidosis: Deposition of amyloid within astrocytes, a glial subtype, which may amplify local Aβ production and inflammatory signalling.

Long non-coding RNA BACE1-AS: A regulatory RNA molecule that stabilises β-site APP-cleaving enzyme 1 (BACE1) transcripts, promoting Aβ formation under stress conditions.

Microglial activation: The process by which brain-resident immune cells adopt a proinflammatory phenotype, affecting Aβ clearance and neuronal support.

References

1. Astrocytes in Amyloid Generation and Alcohol Metabolism: Implications of Alcohol Use in Neurological Disorder(s). Cells (2024).
2. Alcohol as a Modifiable Risk Factor for Alzheimer’s Disease—Evidence from Experimental Studies. International Journal of Molecular Sciences (2023).
3. Adolescent Binge Alcohol Enhances Early Alzheimer’s Disease Pathology in Adulthood Through Proinflammatory Neuroimmune Activation. Frontiers in Pharmacology (2022).
4. Chronic Ethanol Causes Persistent Increases in Alzheimer’s Tau Pathology in Female 3xTg-AD Mice: A Potential Role for Lysosomal Impairment. Frontiers in Behavioral Neuroscience (2022).
5. Modulation of hepatic amyloid precursor protein and lipoprotein receptor-related protein 1 by chronic alcohol intake: Potential link between liver steatosis and amyloid-β. Frontiers in Physiology (2022).