Amyloid beta (Aβ) follows a sigmoidal time function with varying accumulation rates. We studied how the position on this function, reflected by different Aβ accumulation phases, influences ɛ4’s association with Aβ and cognitive decline in 503 participants without dementia using Aβ-PET imaging over 5.3-years. First, Aβ load and accumulation were analyzed irrespective of phases using linear mixed regression. Generally, ɛ4 carriers displayed a higher Aβ load. Moreover, Aβ normal (Aβ-) ɛ4 carriers demonstrated higher accumulation. Next, we categorized accumulation phases as “decrease”, “stable”, or “increase” based on trajectory shapes. After excluding the Aβ-/decrease participants from the initial regression, the difference in accumulation attributable to genotype among Aβ- individuals was no longer significant. Further analysis revealed that in increase phases, Aβ accumulation was higher among noncarriers, indicating a genotype-related timeline shift. Finally, cognitive decline was analyzed across phases and was already evident in the Aβ-/increase phase. Our results encourage early interventions for ɛ4 carriers and imply that monitoring accumulating Aβ- individuals might help identify those at risk for cognitive decline.

中文翻译：

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β 淀粉样蛋白积累的轨迹——揭示与 APOE 基因型和认知能力下降的关系

β 淀粉样蛋白 (Aβ) 遵循 S 形时间函数，具有不同的积累率。我们在 5.3 年的时间内使用 Aβ-PET 成像研究了由不同 Aβ 积累阶段反映的该功能的位置如何影响 ɛ4 与 Aβ 的关联以及 503 名未患痴呆症的参与者的认知能力下降。首先，使用线性混合回归分析 Aβ 负荷和积累，无论其处于哪个阶段。一般来说，ɛ4 载体表现出较高的 Aβ 负载。此外，Aβ正常（Aβ-）ɛ4携带者表现出更高的积累。接下来，我们根据轨迹形状将积累阶段分为“减少”、“稳定”或“增加”。从初始回归中排除 Aβ-/减少参与者后，Aβ- 个体之间归因于基因型的积累差异不再显着。进一步分析表明，在增加阶段，非携带者中 Aβ 积累较高，表明与基因型相关的时间线变化。最后，对各个阶段的认知下降进行了分析，并且在 Aβ-/增加阶段已经很明显。我们的结果鼓励对 ɛ4 携带者进行早期干预，并意味着监测累积的 Aβ- 个体可能有助于识别那些有认知能力下降风险的人。