Which sequence best describes the amyloid cascade hypothesis in Alzheimer's disease?

Which sequence best describes the amyloid cascade hypothesis in Alzheimer's disease?

• A. Tau tangles initiate beta-amyloid deposition, driving disease.
• B. Beta-amyloid deposition initiates a cascade leading to tau hyperphosphorylation, neurofibrillary tangles, neuronal loss, and cognitive decline; therapies target amyloid or tau.
• C. Neurodegeneration occurs first, followed by tau tangles and beta-amyloid.
• D. Vascular factors are the sole drivers with no amyloid involvement.

Answer: (B)

The idea being tested is that beta-amyloid deposition starts a chain of events that drives Alzheimer’s disease. Beta-amyloid peptides accumulate outside neurons, forming plaques that disrupt cell function. This buildup then triggers tau protein to become hyperphosphorylated, causing tau to dissociate from microtubules and form neurofibrillary tangles inside neurons. As these tau changes accumulate, neurons lose structure and function, leading to synaptic failure, neuronal death, and the cognitive symptoms of the disease. Because this sequence places beta-amyloid at the origin and tau pathology and neural loss downstream, therapies are often aimed at reducing beta-amyloid production or clearance or directly targeting tau pathology. Other scenarios—placing tau tangles before beta-amyloid, or implicating neurodegeneration without amyloid involvement, or focusing solely on vascular factors—do not align with the cascade model.

The idea being tested is that beta-amyloid deposition starts a chain of events that drives Alzheimer’s disease. Beta-amyloid peptides accumulate outside neurons, forming plaques that disrupt cell function. This buildup then triggers tau protein to become hyperphosphorylated, causing tau to dissociate from microtubules and form neurofibrillary tangles inside neurons. As these tau changes accumulate, neurons lose structure and function, leading to synaptic failure, neuronal death, and the cognitive symptoms of the disease. Because this sequence places beta-amyloid at the origin and tau pathology and neural loss downstream, therapies are often aimed at reducing beta-amyloid production or clearance or directly targeting tau pathology. Other scenarios—placing tau tangles before beta-amyloid, or implicating neurodegeneration without amyloid involvement, or focusing solely on vascular factors—do not align with the cascade model.