Alzheimer Disease and Dementia

Overview of Dementia

• Not a disease: Refers to a set of symptoms, such as poor memory and difficulty in learning new information.
• Causes: Often results from damage to brain cells due to various diseases.

Alzheimer Disease

• Most common cause of dementia.
• Type: Neurodegenerative disease that leads to loss of neurons in the brain, especially in the cortex.

Causes and Pathophysiology

Amyloid Plaques

• Amyloid Precursor Protein (APP):
  • Located in the neuron's cell membrane.
  • Assists in neuron growth and repair.
  • Usually broken down by alpha and gamma secretases.
• Problematic Enzyme Processing:
  • Beta secretase teams up with gamma secretase, creating insoluble amyloid beta monomers.
  • Monomers form beta-amyloid plaques outside neurons, hindering neuron signaling and possibly causing inflammation.
  • Plaques can also lead to amyloid angiopathy, weakening blood vessel walls, increasing hemorrhage risk.

Neurofibrillary Tangles

• Tau Protein:
  • Maintains microtubule structure in neurons.
  • Kinase activation due to plaques causes tau phosphorylation.
  • Tau becomes sticky, forming tangles inside neurons and disrupting signaling.
• Effects on Neurons:
  • Neurons die, leading to brain atrophy, narrowed gyri, widened sulci, and enlarged ventricles.

Types of Alzheimer Disease

Sporadic Alzheimer Disease

• Characteristics: Late-onset, with mixed genetic and environmental risk factors.
• Prevalence: Increases with age—1% at 60-65 years, 50% over 85 years.
• Risk Factor: APOE-e4 allele contributes to plaque formation.

Familial Alzheimer Disease

• Characteristics: Early-onset, due to dominant gene mutations.
• Prevalence: 5-10% of cases.
• Genetic Causes:
  • PSEN-1 or PSEN-2 gene mutations affect gamma-secretase activity.
  • Trisomy 21 leads to increased APP expression in Down syndrome, accelerating plaque formation.

Progression of Symptoms

• Early Stages: Difficulty detecting symptoms; short-term memory loss.
• Middle Stages: Loss of motor skills, language difficulty, and long-term memory loss.
• Advanced Stages: Disorientation, requiring full-time care, often leads to death by infection (e.g., pneumonia).

Diagnosis and Treatment

• Diagnosis: Difficult; confirmed via brain biopsy post-autopsy.
• Current Treatments:
  • No cure.
  • Existing medications provide limited benefits and do not stop disease progression.