Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Neurobiol Aging. 2018 Nov;71:72-80. doi: 10.1016/j.neurobiolaging.2018.07.007. Epub 2018 Jul 19.
Sporadic Alzheimer's disease (AD) usually presents clinically after 65 years of age, but its pathological changes begin decades earlier. We examined for AD pathology in the postmortem brains of 431 of subjects aged 30-65 years not clinically characterized. Among 40-49 year olds, 15% showed diffuse amyloid β (Aβ) plaques, with a prevalence of 80% in ApoE4/E4, 42% in E4/E3, and <1% in E3/E3 subjects. Aβ deposits appeared after age 49 years in subjects with E3/E3 genotypes. Neuritic plaques first appeared after age 50 years and increased steadily with age in all genotypes. Insoluble Aβ42 levels were highest in parietal, temporal, and frontal lobes, but barely detectable in precuneus. Tau lesions were present in the hippocampus and entorhinal cortex in 7% of subjects aged <40 years and increased steadily with age reaching near 70% in the 60- to 65-year age group. In the locus coeruleus, tau lesions were present in 72% of subjects aged 31-40 years and 94% in the 41- to 50-year age group. Both Aβ and tau lesions are present in the brains of young individuals decades before the age of clinical onset of AD. Aβ lesions closely correlate with the ApoE4 allele and appear as the earliest event in the development of senile plaques.
散发性阿尔茨海默病（AD）通常在 65 岁以后出现临床症状，但病理变化早在几十年前就开始了。我们在 431 名未表现出临床特征的 30-65 岁尸检脑标本中检查 AD 病理。在 40-49 岁的人群中，有 15%出现弥漫性淀粉样β（Aβ）斑块，ApoE4/E4 基因型的患病率为 80%，E4/E3 基因型为 42%，E3/E3 基因型为 <1%。Aβ 沉积在 E3/E3 基因型的个体中出现在 49 岁以后。神经原纤维缠结首先出现在 50 岁以后，在所有基因型中随年龄增长而稳步增加。不可溶性 Aβ42 水平在顶叶、颞叶和额叶最高，但在楔前叶几乎检测不到。在 40 岁以下的受试者中，7%的海马和内嗅皮质出现 Tau 病变，且随年龄增长而稳步增加，在 60-65 岁年龄组中接近 70%。在蓝斑核中，31-40 岁的受试者中有 72%，41-50 岁的受试者中有 94%存在 Tau 病变。在 AD 临床发病前几十年，年轻人的大脑中就存在 Aβ 和 Tau 病变。Aβ 病变与 ApoE4 等位基因密切相关，是老年斑形成的最早事件。
