Alzheimer's Disease Pathophysiology

Alzheimer's Disease Overview

• Affects approximately 7.5 million Americans of all ages
• Characterized by loss of cognitive and physical functioning, often with behavioral symptoms

Genetic Factors

• Late onset AD primarily linked to apolipoprotein E (APOE) genotype
• Genetic-environmental interaction may contribute to AD development
• Young onset AD (<1% of cases) attributed to chromosomal alterations affecting amyloid precursor protein processing

Risk Factors

• Age
• Decreased brain reserve capacity
• Head injury
• Down syndrome
• Depression
• Mild cognitive impairment
• Vascular disease risk factors:
  • Hypertension
  • Elevated homocysteine
  • Elevated low-density lipoprotein cholesterol
  • Low high-density lipoprotein cholesterol
  • Obesity
  • Metabolic syndrome
  • Diabetes

Pathological Characteristics

• Signature lesions:
  • Intracellular neurofibrillary tangles (NFTs)
  • Extracellular plaques in the cortex and medial temporal lobe
  • Neuronal and synaptic degeneration
  • Cortical atrophy
• AD individuals have a higher burden of plaques and NFTs in younger years compared to age-matched controls

Proposed Mechanisms

• β amyloid protein aggregation, leading to plaque formation
• Hyperphosphorylation of tau protein, leading to NFTs
• Synaptic failure and depletion of neurotrophin and neurotransmitters
• Mitochondrial dysfunction
• Oxidative stress
• Amyloid cascade hypothesis: β amyloid production and clearance imbalance, leading to AD

Neurotransmitter Deficit

• Loss of cholinergic activity is the most prominent neurotransmitter deficit, correlating with AD severity
• Cholinergic cell loss is a consequence of AD pathology, not the cause

This quiz covers the pathophysiology of Alzheimer's disease, including its genetic susceptibility, environmental interactions, and rare forms of the disease that occur at a young age.