Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Foundation Trust, UK.
Division of Psychiatry, University College London, London, UK; Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neurosciences, King's College London, London, UK; The LonDownS Consortium, London, UK.
Free Radic Biol Med. 2018 Jan;114:3-9. doi: 10.1016/j.freeradbiomed.2017.08.024. Epub 2017 Sep 1.
Alzheimer's disease (AD) may affect in excess of 90% of individuals with Down syndrome (DS) after age 60, due to duplication of the APP gene in trisomy of chromosome 21, with neuropathology that is comparable to Sporadic AD and Familial AD (FAD). Previous literature suggested some unique features in clinical presentation of dementia in DS (DSd), which might be due to diagnostic difficulties, or represent a real difference compared to SAD or FAD. We review current knowledge on clinical diagnosis and presentation of dementia in DS in comparison with FAD due to APP mutations and APP duplication. We suggest that the clinical presentation in DS (prominent memory decline and behavioral symptoms, and early development of myoclonus and seizures) are similar to the clinical features associated with APP mutations that is known to have an increased Aβ42/ Aβ40 ratio, and highlight the relative lack of vascular complications associated with cerebral amyloid angiopathy in DS in comparison with those rare individuals with FAD due to duplication APP. We consider the biomarker evidence associated with DS and DSd with reference to Aβ peptide levels and oxidative stress, and suggest future directions for research to explore the potential mechanisms associated with the clinical presentation of DSd.
阿尔茨海默病（AD）可能会影响超过 90%的唐氏综合征（DS）患者，年龄超过 60 岁，这是由于 21 号染色体三体性中 APP 基因的重复，其神经病理学与散发性 AD 和家族性 AD（FAD）相当。先前的文献表明，DS 痴呆的临床表现存在一些独特的特征（DSd），这可能是由于诊断困难，或者与 SAD 或 FAD 相比代表真正的差异。我们回顾了由于 APP 突变和 APP 重复导致的与 FAD 相比，DS 中痴呆的临床诊断和表现的现有知识。我们认为，DS 中的临床表现（明显的记忆减退和行为症状，以及肌阵挛和癫痫的早期发作）与已知 Aβ42/Aβ40 比值增加的 APP 突变相关的临床特征相似，并强调与那些由于 APP 重复而患有 FAD 的罕见个体相比，DS 中与脑淀粉样血管病相关的血管并发症相对较少。我们考虑了与 DS 和 DSd 相关的生物标志物证据，参考 Aβ肽水平和氧化应激，并提出了未来的研究方向，以探索与 DSd 临床表现相关的潜在机制。
