In recent years, a growing number of scientific studies have backed an alarming hypothesis: Alzheimer's disease isn't just a disease, it's an infection.

近年来，越来越多的科学研究都证明了一个惊人的假设：阿尔茨海默病并非仅仅是一种疾病，它还是一种感染。

While the exact mechanisms of this infection are something researchers are still trying to isolate, numerous studies suggest the deadly spread of Alzheimer's goes way beyond what we used to think.

尽管研究人员仍在尝试分离造成感染的精确机制，但是众多研究表明，阿尔茨海默病的致命传播完全超出了我们的想象。

One such study, published in 2019, suggested what could be one of the most definitive leads yet for a bacterial culprit behind Alzheimer's, and it comes from a somewhat unexpected quarter: gum disease.

2019年发表的这样一项研究表明，引起阿尔茨海默病的细菌可能是最明确的罪魁祸首之一，这个细菌的来源有点出人意料：牙周病。

In a paper led by senior author Jan Potempa, a microbiologist from the University of Louisville, researchers reported the discovery of Porphyromonas gingivalis – the pathogen behind chronic periodontitis (aka gum disease) – in the brains of deceased Alzheimer's patients.

在一篇以Jan Potempa，资深作者、路易斯维尔大学微生物学家领导的论文中，研究人员在去世的阿尔茨海默病患者的大脑中发现了牙龈卟啉单胞菌-一种导致慢性牙周病的病原体。

It wasn't the first time the two factors have been linked, but the researchers went further.

这已经不是第一次将这两个因素联系在一起了，但是研究人员在这个基础上又进行了深入的研究。

In separate experiments with mice, oral infection with the pathogen led to brain colonization by the bacteria, together with increased production of amyloid beta (Aβ), the sticky proteins commonly associated with Alzheimer's.

在一项针对老鼠的单独试验中，口腔细菌感染会导致细菌在大脑中定殖并同时会产生更多的淀粉样蛋白（Aβ）-一种通常与阿尔茨海默病相关的粘稠蛋白质。

The research team, coordinated by pharma startup Cortexyme, which was co-founded by first author Stephen Dominy, wasn't claiming to have discovered definitive evidence of Alzheimer's causation.

由第一作者Stephen Domity联合创办的医药初创公司Cortexyme所牵头的研究团队并未宣传其已经发现了造成阿尔茨海默病的确切证据。

But it was clear they thought we had a strong line of investigation here.

但显而易见的是，他们认为我们已经有了强有力的调查线索。

"Infectious agents have been implicated in the development and progression of Alzheimer's disease before, but the evidence of causation hasn't been convincing," Dominy said at the time.

Dominy表示，“传染性物质曾经被认为与阿尔茨海默病的发生和加重有关，但是关于成因却一直缺乏令人信服的证据。”

"Now, for the first time, we have solid evidence connecting the intracellular, Gram-negative pathogen, P. gingivalis, and Alzheimer's pathogenesis."

“现在，我们首次有充分证据表明，细胞内革兰氏阴性病原体-牙龈卟啉菌与阿尔茨海默病的发病机制有关。”

Pathogenesis：发病机制

In addition, the team identified toxic enzymes called gingipains secreted by the bacteria in the brains of Alzheimer's patients, which correlated with two separate markers of the disease: the tau protein, and a protein tag called ubiquitin.

此外，团队还发现了一种被称为牙龈素的有毒的酶，这种酶是阿尔茨海默病患者大脑中的细菌所分泌的。这种酶与两种不同的疾病标志物有关联：tau蛋白和一种被称为泛素的蛋白标记。

But even more compellingly, the team identified these toxic gingipains in the brains of deceased people who were never diagnosed with Alzheimer's.

但是，更加令人信服的是，团队在从未被诊断为阿尔茨海默病的逝者的大脑中发现了这些有毒的牙龈素。

That's important, because while P. gingivalis and the disease have been linked before, it's never been known – to put it simply – whether gum disease causes Alzheimers, or whether dementia leads to poor oral care.

这一点很重要，因为尽管牙龈卟啉菌曾经与阿尔茨海默病联系在一起，但是有一点却始终无从知晓-简单说来-就是到底是牙周炎引起了阿尔茨海默病，还是痴呆导致口腔护理不到位。

The fact that low levels of gingipains were evident even in people who were never diagnosed with Alzheimer's could be a smoking gun – suggesting they might have developed the condition if they had lived longer.

在从未被诊断为阿尔茨海默病的逝者的大脑中发现少量的牙龈素这一事实可能就是明确的证据-这一证据表明，如果这些逝者活得再久一些，他们就可能会患上阿尔茨海默病。

"Our identification of gingipain antigens in the brains of individuals with AD and also with AD pathology but no diagnosis of dementia argues that brain infection with P. gingivalis is not a result of poor dental care following the onset of dementia or a consequence of late-stage disease, but is an early event that can explain the pathology found in middle-aged individuals before cognitive decline," the authors explained in their paper.

“我们在阿尔茨海默病逝者以及存在阿尔茨海默病病理但未被诊断为阿尔茨海默病逝者的大脑中发现的牙龈素抗原证明，大脑感染牙龈卟啉菌并非是由于出现痴呆之后口腔卫生护理不到位或者病程后期所导致的结果，而是早期的一个现象，这就可以解释了在出现认知下降之前的中年人中所发现的病理学。”

Further, a compound formulated by the company called COR388, showed in experiments with mice that it could reduce bacterial load of an established P. gingivalis brain infection, while also reducing amyloid-beta production and neuroinflammation.

此外，一种由公司研发的复合物-COR388在一项针对老鼠的实验中表明，它可以减少已确定的牙龈卟啉菌大脑感染的细菌量，并同时减少淀粉样蛋白-β的产生和神经炎症。

We'll have to wait and see what future research will uncover about this link, but the research community is cautiously optimistic.

我们还需要继续等待，看看未来的研究在这一关联中还能获得哪些发现，但是研究届对此持谨慎乐观的态度。

"Drugs targeting the bacteria's toxic proteins have so far only shown benefit in mice, yet with no new dementia treatments in over 15 years it's important that we test as many approaches as possible to tackle diseases like Alzheimer's," chief scientific officer David Reynolds from Alzheimer's Research commented in a statement.

阿尔茨海默病研究中心的首席科学官David Reynolds在声明中评论说：“针对细菌中有毒蛋白质的药物至今只在老鼠身上看到了效果，但是，在15年里都没有治疗痴呆症的新疗法的情况下，我们要尽可能多的尝试各种方法来治疗像阿尔茨海默病这样的疾病。”

原文来源：ScienceAlert

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