Phases of Aβ buildup in Alzheimer’s disease brain

In vivo neuroimaging data from neuropathological studies show a spatiotemporal development of Aβ deposits in the brain, which originates in the cerebral regions and spreads from the neocortex, to the allocortex, to the brainstem, finally reaching the cerebellum.^1,2 Aβ aggregation involves the formation of monomers and oligomers, which then develop into Aβ fibrils and plaques.³ Aβ₄₀ and Aβ₄₂ are the main components of Aβ aggregation, however Aβ₄₂ aggregates into fibrils faster than Aβ₄₀.³ Aβ accumulation in various brain regions results in a cascade of brain damage including abnormal tau phosphorylation, and dysfunction in neuronal physiology (i.e., oxidative stress, mitochondrial dysfunction, neuroinflammation, and impaired brain plasticity).³

References:
1. Hampel H, Hu Y, Hardy J, et al. The amyloid-β pathway in Alzheimer’s disease: a plain language summary. Neurodegener Dis Manag 2023. doi: 10.2217/nmt-2022-0037.

2. Thal DR, Rüb U, Orantes M, Braak H. Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 2002; 58 (12): 1791–1800.

3. Fišar Z. Linking the amyloid, tau, and mitochondrial hypotheses of Alzheimer’s Disease and identifying promising drug targets. Biomolecules 2022; 12 (11): 1676.