Sokol Deborah K, Lahiri Debomoy K
Section of Pediatrics, Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, United States.
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States.
Front Mol Neurosci. 2023 Sep 22;16:1201723. doi: 10.3389/fnmol.2023.1201723. eCollection 2023.
Recent studies promote new interest in the intersectionality between autism spectrum disorder (ASD) and Alzheimer's Disease. We have reported high levels of Amyloid-β Precursor Protein (APP) and secreted APP-alpha (sAPP) and low levels of amyloid-beta (Aβ) peptides 1-40 and 1-42 (Aβ40, Aβ42) in plasma and brain tissue from children with ASD. A higher incidence of microcephaly (head circumference less than the 3 percentile) associates with ASD compared to head size in individuals with typical development. The role of Aβ peptides as contributors to acquired microcephaly in ASD is proposed. Aβ may lead to microcephaly via disruption of neurogenesis, elongation of the G1/S cell cycle, and arrested cell cycle promoting apoptosis. As the APP gene exists on Chromosome 21, excess Aβ peptides occur in Trisomy 21-T21 (Down's Syndrome). Microcephaly and some forms of ASD associate with T21, and therefore potential mechanisms underlying these associations will be examined in this review. Aβ peptides' role in other neurodevelopmental disorders that feature ASD and acquired microcephaly are reviewed, including dup 15q11.2-q13, Angelman and Rett syndrome.
近期研究引发了人们对自闭症谱系障碍（ASD）与阿尔茨海默病之间交叉性的新兴趣。我们报告称，自闭症谱系障碍儿童的血浆和脑组织中，淀粉样前体蛋白（APP）和分泌型APP-α（sAPP）水平较高，而淀粉样β（Aβ）肽1-40和1-42（Aβ40、Aβ42）水平较低。与发育正常个体的头围相比，自闭症谱系障碍患者中头小畸形（头围小于第3百分位数）的发生率更高。有人提出Aβ肽在自闭症谱系障碍所致后天性头小畸形中起作用。Aβ可能通过破坏神经发生、延长G1/S细胞周期以及阻止细胞周期促进细胞凋亡，从而导致头小畸形。由于APP基因位于21号染色体上，21三体综合征（唐氏综合征）中会出现过量的Aβ肽。头小畸形和某些形式的自闭症谱系障碍与21三体综合征相关，因此本综述将研究这些关联背后的潜在机制。本文还综述了Aβ肽在其他以自闭症谱系障碍和后天性头小畸形为特征的神经发育障碍中的作用，包括15q11.2-q13重复、天使综合征和雷特综合征。
