Alzheimer's Disease and Dementia

Alzheimer's Disease (AD)

• Alzheimer's disease is a fatal neurodegenerative disorder affecting 1-2% of the US population.
• In 2015, around 44 million people worldwide had AD, with 4.6 million new cases predicted each year.

Risk Factors

• Three major risk factors for AD: • Age – 65 and over • Gender – female • Family history
• Other risk factors: • Obesity • High blood pressure • Head trauma • High cholesterol • Diabetes • Down syndrome • Living in America • Higher rates in Japanese-Americans and African-Americans • Lower rates in highly educated people • Beneficial consequences of learning and memory

Clinical Symptoms

• Progressive deterioration of memory and cognitive functions
• Loss of autonomy requiring full-time medical care
• Severe neuronal loss
• Aggregation of amyloid β (Aβ) in extracellular senile plaques
• Formation of intraneuronal neurofibrillary tangles consisting of hyperphosphorylated tau protein

Pathogenesis of Alzheimer Disease

• β-amyloid peptide (Aβ) and tau protein deposition in the brain
• Aβ peptide generated from the larger βAPP protein and found in amyloid or senile plaques in the extracellular space of AD brains
• Amyloid plaques also contain other proteins like apoE
• Tau protein expressed in high levels in neurons of the brain
• Hyperphosphorylated forms of tau form inclusions, neurofibrillary tangles, inside AD neurons
• Phosphorylation diminishes tau protein's normal function of promoting the assembly and stability of microtubules

Forms of Dementia

• Alzheimer's disease (>60%)
• Vascular dementia
• Diffuse Lewy body disease (DLBD)
• Parkinson's disease
• Huntington's disease
• Frontotemporal dementia (Pick's disease)
• Progressive Supranuclear Palsy
• Creutzfeldt-Jakob disease
• Normal pressure hydrocephalus