Fig. 2: Summary of Aβ and tau pathology in Alzheimer’s disease.
From: Amyloid-β and Tau in Alzheimer’s disease: pathogenesis, mechanisms, and interplay
AD brain is an atrophic brain characterized by the presence and accumulation of Aβ plaques (mostly extraneuronal) and NFTs within neurons. As shown in the figure, Aβ plaques are usually extraneuronal, surrounded by dystrophic neurites, or may reside in the vicinity of synapses, causing synaptic dysfunction. AD neurons develop dystrophic neurites containing various organelles, accumulated tubulins, and high concentrations of β-secretase. Therefore, rather than other neuronal regions, Aβ peptides are thought to be mainly secreted from dystrophic neurites, which then aggregate as Aβ plaques in interneuronal/extraneuronal space. Functional reactive astrocytes mediate phagocytosis of dystrophic neurites and Aβ plaques to reduce the plaque load and alleviate AD. However, as Aβ plaques continue to rise, they seem to modulate the phagocytic activity of reactive astrocytes through unknown mechanisms, thereby leading to further accumulation of Aβ plaques and exacerbation of AD. On the other hand, tau pathology is an indispensable part of AD pathology. After dissociation from the cytoskeleton, tau proteins form tangles, which then aggregate and propagate throughout neurons, ultimately developing NFTs. In synaptic regions, tau tangles may interfere with axonal transportation.
