Pathophysiology of Alzheimer Disease The two pathologic hallmarks of Alzheimer disease are Extracellular beta-amyloid deposits (in neuritic plaques) Intracellular neurofibrillary tangles (paired helical filaments) The beta-amyloid deposition and neurofibrillary tangles lead to loss of synapses and neurons, which results in gross atrophy of the affected areas of the brain, typically starting at the mesial temporal lobe.