What is the neuropathological hallmark of Alzheimer's disease?

• A. Lewy bodies and demyelination
• B. Amyloid plaques and neurofibrillary tangles with progressive neurodegeneration
• C. Prions
• D. Neuroinflammation without plaques

Answer: (B)

Alzheimer's disease is defined by two main brain changes that drive the disease course: extracellular amyloid plaques and intracellular neurofibrillary tangles, together with progressive neurodegeneration. Amyloid plaques are clumps of amyloid-beta peptide that accumulate outside neurons due to abnormal processing of the amyloid precursor protein, leading to synaptic dysfunction and neuron death. Neurofibrillary tangles form inside neurons from hyperphosphorylated tau, which disrupts microtubule stability and axonal transport, further contributing to neuronal injury. The spread and accumulation of these pathologies, especially in memory-related regions like the hippocampus and cortex, correlate with cognitive decline.

Other conditions have different hallmark lesions—for example, Lewy bodies made of alpha-synuclein characterize Lewy body diseases, and prion diseases involve infectious misfolded proteins that cause distinct spongiform changes. Neuroinflammation can occur in many disorders but does not define Alzheimer's on its own without the characteristic plaques and tangles.