Abstract
INTRODUCTION: This study investigates the association of age and biological sex with Alzheimer's disease (AD) neuropathology in Down syndrome (DS). METHODS: We examined the frontal/occipital cortex in people with DS (n = 14/13, 1-39 years), DS with AD (DSAD) neuropathology (n = 18/19, 42-61 years), late-onset AD (n = 15/16, 72-96 years), and age-matched controls (n = 50/47)(n = 156). The area occupied by AT8 and 6E10 immunolabeling, representing tangle and plaque loads, respectively, was used for segmented linear regression analyses. RESULTS: There was elevated neuropathology after age 35 in DSAD, with inflection points at ∼31 years (amyloid-β [Aβ]) and ∼28 (phosphorylated tau [p-tau]) in the frontal cortex and ∼36 years (both Aβ and p-tau) in the occipital cortex. Occipital p-tau was higher in women relative to men with DS. Aβ and p-tau pathology were correlated in women with DS but not in men with DS in the occipital cortex. DISCUSSION: Women with DS may show a more advanced stage of tau pathology relative to men with DS. HIGHLIGHTS: Amyloid-β (Aβ) and phosphorylated tau (p-tau) Alzheimer's disease (AD) pathology emerge after 30 years of age in the frontal cortex, followed 7 years later by pathology in the occipital cortex in Down syndrome (DS). Women with DS show a more rapid progression of AD neuropathology seen by trends in higher p-tau relative to men, despite similar levels of Aβ. Women with DS show a stronger association between Aβ and tau in the occipital but not frontal cortex relative to men with DS, independent of age.