Andrews Elizabeth J, Ngo Phong T, Pascual Jesse R, Gonzalez Freddy, Phelan Michael, Wright Sierra T, Harp Jordan, Schmitt Frederick, Lai Florence, Lao Patrick J, Brickman Adam M, Kofler Julia, Ikonomovic Milos D, Head Elizabeth
Department of Pathology & Laboratory Medicine, 1111 Gillespie Neuroscience Research Facility, University of California Irvine, Irvine, California, USA.
Department of Neurology, Sanders Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
Alzheimers Dement. 2025 Jul;21(7):e70408. doi: 10.1002/alz.70408.
This study investigates the association of age and biological sex with Alzheimer's disease (AD) neuropathology in Down syndrome (DS).
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.
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.
Women with DS may show a more advanced stage of tau pathology relative to men with DS.
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.
本研究调查了唐氏综合征（DS）患者的年龄和生物性别与阿尔茨海默病（AD）神经病理学之间的关联。
我们检查了DS患者（n = 14/13，1 - 39岁）、患有AD神经病理学（DSAD）的DS患者（n = 18/19，42 - 61岁）、晚发性AD患者（n = 15/16，72 - 96岁）以及年龄匹配的对照组（n = 50/47）（n = 156）的额叶/枕叶皮质。分别代表缠结和斑块负荷的AT8和6E10免疫标记所占据的面积用于分段线性回归分析。
DSAD患者在35岁后神经病理学有所升高，额叶皮质中淀粉样β蛋白（Aβ）的拐点约为31岁，磷酸化tau蛋白（p - tau）的拐点约为28岁，枕叶皮质中Aβ和p - tau的拐点约为36岁。患有DS的女性枕叶p - tau相对于男性更高。在枕叶皮质中，患有DS的女性Aβ和p - tau病理学相关，而患有DS的男性则不相关。
患有DS的女性相对于患有DS的男性可能表现出更晚期的tau病理学阶段。
在唐氏综合征（DS）中，额叶皮质在30岁后出现淀粉样β蛋白（Aβ）和磷酸化tau蛋白（p - tau）阿尔茨海默病（AD）病理学，7年后枕叶皮质出现病理学。患有DS的女性尽管Aβ水平相似，但相对于男性，p - tau水平较高，显示出AD神经病理学进展更快。相对于患有DS的男性，患有DS的女性在枕叶皮质而非额叶皮质中Aβ和tau之间的关联更强，与年龄无关。
