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2 AD In the early 20th century, German psychiatrist Alois Alzheimer, using silver-staining techniques on the brain tissue of a patient with cognitive decline, first described two hallmark lesions: extracellular senile plaques composed of -amyloid deposits and intraneuronal neurofibrillary tangles ( The traditional amyloid cascade hypothesis posits that A oligomers are the central pathogenic initiators in AD