Neuropathology of Alzheimer's Disease and its Variants

Alzheimer's disease is defined by parenchymal deposits of Aβ peptide, and by intracellular accumulation of tau protein, accompanied by cerebral atrophy, particularly affecting the hippocampus and parahippocampal gyrus, with variable ventricular dilation. Aβ peptide, cleaved from the amyloid precursor protein (APP) by β-and γ-secretase enzymes, accumulates mainly extracellularly, as diffuse or focal deposits. Aβ peptide is also the main constituent of cerebral amyloid angiopathy, thought to be due to deficits in clearance of Aβ in the vessel walls. Tau protein accumulates in neurons as neurofibrillary tangles (neuronal cell body), neuropil threads (mainly dendrites) and degenerating neurites of the corona of the neuritic plaque. Synaptic and neuronal losses are important pathogenetic mechanisms, but difficult to routinely assess. Neuroinflammation could also play an important role. In additon to pathology associated with neuropathology of Alzheimer's disease and its variants, its differential diagnosis is also considered.