Scientists at the University of California, Riverside, have a new idea about Alzheimer's disease. They think two proteins in the brain fight each other.

加州大學河濱分校的科學家對阿茲海默症有了新想法。他們認為大腦中的兩種蛋白質在互相對抗。

For a long time, doctors looked at protein clumps outside the cells. But medicines to remove these clumps did not work. Now, scientists look inside the cells.

長期以來，醫生一直關注細胞外的蛋白質聚集物。但使用藥物清除這些聚集物並沒有效果。現在，科學家開始研究細胞內的情況。

Inside the cell, two proteins are called amyloid beta and tau. They both want to stick to small tubes. These tubes move food and materials in the brain. Amyloid beta pushes tau away from the tubes. This breaks the transport system.

在細胞內，有兩種蛋白質被稱為 β-類澱粉蛋白和 tau 蛋白。它們都想附著在小管上。這些小管負責在大腦中輸送營養和物質。β-類澱粉蛋白會將 tau 蛋白從小管上推開，導致運輸系統損壞。

As people get old, their cells do not clean themselves well. This means more amyloid beta stays in the cell. This makes the problem worse. Some medicines like lithium might help stop this.

隨著年齡增長，細胞的自我清理能力下降。這意味著有更多的 β-類澱粉蛋白留在細胞內，使問題更加嚴重。某些藥物（如鋰鹽）可能會幫助阻止這種情況。

Scientists now want to protect the tubes in the brain. They also want to help cells clean themselves better.

科學家現在希望保護大腦中的小管，並幫助細胞地更好地進行自我清理。

Researchers at the University of California, Riverside, have proposed a new theory suggesting that Alzheimer's disease starts because of a conflict between two proteins, amyloid beta and tau, inside brain cells.

加州大學河濱分校的研究人員提出了一個新理論，認為阿茲海默症是因為腦細胞內兩種蛋白質——β-澱粉樣蛋白與 tau 蛋白之間產生衝突而引起的。

For a long time, scientists believed that amyloid beta plaques outside the cells were the primary cause of the disease. However, many clinical trials failed to help patients after removing these plaques, which suggests that the plaques might be a result of the disease rather than the cause. Consequently, researchers are now focusing on what happens inside the neurons.

長期以來，科學家認為細胞外的 β-澱粉樣蛋白斑塊是此病的主因。然而，許多臨床試驗在清除這些斑塊後仍無法幫助患者，這顯示斑塊可能是疾病的結果而非原因。因此，研究人員現在將焦點轉向神經元內部發生的情況。

A recent study published in the Proceedings of the National Academy of Sciences, Nexus, explains that amyloid beta and tau proteins compete to attach to microtubules, which are essential for transporting nutrients within the cell. The team found that amyloid beta can push tau away from these microtubules. This process destabilizes the cell's transport system and causes tau to clump together abnormally. Furthermore, as people age, the body's ability to clean out cellular waste decreases, which allows more amyloid beta to build up and increase this competition.

最近發表在《美國國家科學院科學報告》Nexus 的研究解釋，β-澱粉樣蛋白與 tau 蛋白會競爭附著在微管上，而微管對於細胞內輸送營養至關重要。研究團隊發現，β-澱粉樣蛋白會將 tau 蛋白從這些微管上推開。這個過程會使細胞的輸送系統變得不穩定，並導致 tau 蛋白異常凝集。此外，隨著人們年齡增長，身體清理細胞廢物的能力下降，導致更多 β-澱粉樣蛋白積聚並增加這種競爭。

Experts in the field have responded with caution. Michael Kane from the Indiana Center for Recovery asserted that while this model is biologically possible and improves current theories, it is not yet clinical proof. He emphasized that scientists must first confirm these processes in human patients to prove they actually lead to memory loss and cognitive decline.

該領域的專家對此反應較為謹慎。印第安納康復中心的 Michael Kane 指出，雖然這個模型在生物學上是可行的，且改善了現有理論，但尚未有臨床證明。他強調，科學家必須先在人類患者身上確認這些過程，以證明它們確實會導致記憶力喪失與認知能力下降。

Current research suggests a shift toward studying how proteins interact inside the cell. This could lead to new treatments that focus on protecting microtubules and improving how cells clear out waste.

目前的研究建議將焦點轉向研究蛋白質在細胞內部如何互動。這可能會帶來新的治療方法，重點將放在保護微管及改善細胞清理廢物的方式。

Researchers at the University of California, Riverside, have proposed a theoretical model suggesting that Alzheimer's disease originates from the intracellular interference between amyloid beta and tau proteins.

加州大學河濱分校的研究人員提出了一項理論模型，認為阿茲海默症源於細胞內 beta-類澱粉蛋白與 tau 蛋白之間的干擾。

Historically, the amyloid hypothesis has dominated the field, predicated on the observation that amyloid beta (a-beta) aggregates correlate with the disease. This paradigm was reinforced by genetic evidence linking increased a-beta levels to early-onset cases. However, the systemic failure of numerous clinical trials aimed at the removal of these extracellular plaques suggests that such aggregates may be symptomatic rather than causative.

在過去，類澱粉質假說一直主導著該領域，其基礎在於觀察到 beta-類澱粉蛋白（a-beta）的聚集與疾病相關。這一範式隨後被基因證據強化，將 a-beta 水平增加與早發性病例聯繫起來。然而，許多旨在清除這些細胞外斑塊的臨床試驗系統性失敗，顯示此類聚集物可能是症狀而非致病原因。

Recent findings published in the Proceedings of the National Academy of Sciences, Nexus, shift the analytical focus toward the intracellular environment. The study identifies a competitive interaction between a-beta and tau proteins regarding their binding to microtubules—essential structural conduits for nutrient and material transport within neurons. Through the application of fluorescent markers, the research team demonstrated that a-beta possesses a binding affinity for microtubules comparable to that of tau. Consequently, the accumulation of a-beta may displace tau, thereby destabilizing the neuron's internal transport mechanism and inducing tau to aggregate abnormally.

近期發表於《美國國家科學院論文集》（PNAS）Nexus 的研究結果，將分析焦點轉向細胞內環境。該研究發現 a-beta 與 tau 蛋白在結合微管（神經元內營養與物質輸送的關鍵結構通道）方面存在競爭互動。研究團隊透過螢光標記證明，a-beta 對微管的結合親和力與 tau 相當。因此，a-beta 的積聚可能會取代 tau，從而導致神經元內部輸送機制不穩定，並誘導 tau 異常聚集。

This mechanism is further contextualized by the decline of autophagy, the cellular recycling process, which diminishes with senescence. A reduction in autophagic efficiency facilitates the intracellular accumulation of a-beta, increasing the probability of tau displacement. Furthermore, the researchers noted a potential correlation with lithium's known microtubule-stabilizing properties, which may mitigate the risks associated with this protein competition.

此機制進一步與自噬作用（細胞回收過程）的衰退相關，而自噬功能會隨著老化而減少。自噬效率的降低促使 a-beta 在細胞內積聚，增加了 tau 被取代的機率。此外，研究人員注意到這與鋰離子已知的微管穩定特性可能存在相關性，而鋰離子或許能降低這種蛋白質競爭相關的風險。

Stakeholder perspectives remain cautious. While Michael Kane of the Indiana Center for Recovery acknowledges the biological plausibility of this model as a refinement of existing theories, he emphasizes that a plausible mechanism does not constitute clinical proof. The transition from a theoretical model to a therapeutic application requires empirical confirmation of these processes within human patients and their correlation with cognitive decline.

相關利益者的看法仍保持謹慎。印第安納康復中心的 Michael Kane 承認此模型作為現有理論的改良在生物學上具有可行性，但他強調，可行的機制並不等同於臨床證明。從理論模型轉向治療應用，需要對人類患者體內的這些過程及其與認知能力下降的相關性進行實證確認。

The current state of research indicates a shift toward examining intracellular protein dynamics, potentially redirecting future therapeutic strategies toward microtubule protection and the enhancement of cellular clearance mechanisms.

目前的研究狀態顯示趨勢正轉向檢視細胞內蛋白質動力學，未來可能會將治療策略重新導向至微管保護與強化細胞清除機制。