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. Author manuscript; available in PMC: 2021 Apr 22.
Published in final edited form as: Nat Rev Neurol. 2019 Mar;15(3):135–147. doi: 10.1038/s41582-018-0132-6

Figure 6. Hypothetical progression of Alzheimer disease neuropathology in Down syndrome.

Figure 6.

A proposed timeline from birth to over 60 years of age of Alzheimer disease (AD) pathology in individuals with Down syndrome (DS). Mitochondrial dysfunction and increased generation of reactive oxygen species (ROS) occurs as early as in fetal brain. Brain inflammation can begin as early as in the late teens with the presence of activated microglial cells, which are associated with Aβ plaques later in the disease. By age 40 years, both extracellular Aβ and NFTs are present in sufficient quantities for a neuropathological diagnosis of AD. As individuals with DS age to over 50 years, AD neuropathology increases in severity and clinical signs of dementia become frequent.