Notes on Alzheimer's Disease and Dementia

Overview of Dementia

• Definition: Dementia is not a disease but a set of symptoms affecting memory, learning, and independent functioning.
• Causes: Usually caused by damage to brain cells, stemming from various diseases.

Alzheimer's Disease

• Common Cause of Dementia: Alzheimer's disease (now referred to as Alzheimer disease) is the most prevalent cause of dementia.
• Nature of the Disease: It is a neurodegenerative disease leading to the degeneration of neurons, particularly in the cortex.
• Symptoms: Characteristic symptoms of dementia due to neuron loss.

Pathophysiology of Alzheimer's Disease

• Key Components: The two major contributors to Alzheimer's progression are plaques and tangles.

Amyloid Beta Plaques

• Amyloid Precursor Protein (APP): A molecule in the neuron membrane crucial for neuron growth and repair.
  • Breaks down normally via alpha and gamma secretases.
  • If beta secretase is involved, it produces amyloid beta monomers that form sticky clumps known as beta amyloid plaques.
• Impact of Plaques:
  • Can disrupt neuron signaling, impairing memory functions.
  • Trigger immune responses leading to inflammation and potential damage to surrounding neurons.
  • Can cause amyloid angiopathy, weakening blood vessel walls and increasing hemorrhage risk.
• Visual Evidence: Histology images show amyloid plaques outside cells.

Neurofibrillary Tangles

• Role of Tau Protein: Neurons' cytoskeleton is partly made of microtubules supported by tau proteins.
• Mechanism of Tangle Formation:
  • Amyloid plaque buildup activates kinase, altering the tau protein's shape.
  • Resulting in tau tangling and neuron dysfunction.
• Consequences: Neurons with tangles struggle with signaling and may undergo apoptosis (cell death).
• Visual Evidence: Histology images display neurofibrillary tangles inside neurons.

Brain Changes Due to Alzheimer's

• Atrophy: As neurons die, the brain shrinks, causing gyri to narrow and sulci to widen, leading to larger ventricles.

Types of Alzheimer's Disease

• Sporadic Alzheimer Disease:

  • Late-onset type with unclear causes; likely influenced by genetic and environmental factors.
  • Risk increases significantly with age (1% at 60-65 years, 50% at over 85).
  • APOE E4 allele: Identified as increasing Alzheimer's risk; inherits one or two alleles raises risk.

• Familial Alzheimer Disease:

  • Early-onset type caused by dominant gene inheritance.
  • Accounts for 5-10% of cases, linked to mutations in PSEN1 and PSEN2 genes.
  • Trisomy 21: Down syndrome involves an extra copy of chromosome 21, increasing APP, thus amyloid plaque buildup.

Symptoms Progression

• Early Stages: Symptoms may be undetectable, progressing to short-term memory loss.
• Intermediate Stages: Loss of motor skills, language difficulties, and eventual long-term memory loss.
• Late Stages: Bedridden condition and increased risk of infections, leading to possible death from pneumonia.

Diagnosis and Treatment

• Diagnosis: Challenging; definitive diagnosis via brain biopsy post-autopsy, typically diagnosed by excluding other dementia causes.
• Current Treatments: No cure; some medications exist but offer minimal benefits and no definitive halt on disease progression.