Fig. 2

Immunostaining with mAb 4G8 detecting β amyloid in plaques and mAb Tau-1 detecting abnormally phosphorylated tau protein in NFTs illustrates staging of β amyloidosis and neurofibrillary degeneration in four individuals with Down syndrome including 28 years old subject with no signs of dementia, Braak stage I with a few NFTs in the entorhinal cortex but significant β amyloidosis in the entorhinal cortex, hippocampus, temporal, and cerebellar cortex corresponding to final Thal phase 5. Progression of neurofibrillary degeneration observed in 41-year-old DS subject with no signs of dementia (Braak stage IV and Thal phase 5), and in 54-year-old DS subject with mild dementia (Braak stage VI and Thal phase 5), reflects topographic expansion and more severe neurofibrillary degeneration and β amyloidosis in the entorhinal cortex, hippocampus, and temporal cortex. Severe β amyloidosis affects molecular layer of the cerebellar cortex in 41- and 54-year-old subjects. In 65-year-old DS subject diagnosed with moderate severe dementia the number of neurons, including neurons with NFTs, and amyloid load in the temporal and cerebellar cortex decrease but pathology still meets criteria for diagnosis of Braak stage VI and Thal phase 5