Alzheimer's Disease: Risk Factors, Pathology, and Prevention Strategies

Alzheimer's disease (AD) is a neurodegenerative disorder with multifactorial etiology. Key risk factors and mechanisms:

Non-Modifiable Risks

• Age: Greatest risk factor; prevalence doubles every 5 years after 65.
• Genetics: APOE ε4 allele (strongest late-onset risk); rare autosomal dominant mutations (APP, PSEN1, PSEN2) cause early-onset familial AD.
• Family history.

Pathological Hallmarks

• Amyloid-β plaques: Extracellular aggregates disrupting synaptic function.
• Neurofibrillary tangles: Hyperphosphorylated tau protein inside neurons, impairing transport.
• Neuronal loss & atrophy: Hippocampus and cortex.
• Neuroinflammation: Microglial activation, cytokine release.

Modifiable Risks (Lifestyle/Vascular)

• Physical inactivity.
• Poor diet (high saturated fat, sugar; low Mediterranean diet adherence).
• Hypertension, diabetes, dyslipidemia, smoking.
• Low cognitive engagement, social isolation.
• Hearing loss, depression, traumatic brain injury.

Prevention

No guaranteed prevention, but evidence supports: regular aerobic exercise, Mediterranean/MIND diet, cognitive stimulation, social engagement, vascular risk control, hearing aids, quality sleep. Early detection via biomarkers (amyloid PET, CSF p-tau) is evolving.