The Center of Traditional Chinese Medicine, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
CNS Neurosci Ther. 2024 Jul;30(7):e14860. doi: 10.1111/cns.14860.
Alzheimer's disease (AD) pathology is featured by the extracellular accumulation of amyloid-β (Aβ) plaques and intracellular tau neurofibrillary tangles in the brain. We studied whether Aβ and tau accumulation are independently associated with future cognitive decline in the AD continuum.
Data were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) public database. A total of 1272 participants were selected based on the availability of Aβ-PET and CSF tau at baseline and of those 777 participants with follow-up visits.
We found that Aβ-PET and CSF tau pathology were related to cognitive decline across the AD clinical spectrum, both as potential predictors for dementia progression. Among them, Aβ-PET (A + T- subjects) is an independent reliable predictor of longitudinal cognitive decline in terms of ADAS-13, ADNI-MEM, and MMSE scores rather than tau pathology (A - T+ subjects), indicating tau accumulation is not closely correlated with future cognitive impairment without being driven by Aβ deposition. Of note, a high percentage of APOE ε4 carriers with Aβ pathology (A+) develop poor memory and learning capacity. Interestingly, this condition is not recurrence in terms of the ADNI-MEM domain when adding APOE ε4 status. Finally, the levels of Aβ-PET SUVR related to glucose hypometabolism more strongly in subjects with A + T- than A - T+ both happen at baseline and longitudinal changes.
In conclusion, Aβ-PET alone without tau pathology (A + T-) measure is an independent reliable predictor of longitudinal cognitive decline but may nonetheless forecast different status of dementia progression. However, tau accumulation alone without Aβ pathology background (A - T+) was not enough to be an independent predictor of cognitive worsening.
阿尔茨海默病（AD）的病理学特征是脑内细胞外的淀粉样β（Aβ）斑块和细胞内的 tau 神经原纤维缠结的积累。我们研究了 Aβ 和 tau 的积累是否与 AD 连续体中未来的认知下降独立相关。
数据来自阿尔茨海默病神经影像学倡议（ADNI）公共数据库。根据基线时 Aβ-PET 和 CSF tau 的可用性以及随访的 777 名参与者，共选择了 1272 名参与者。
我们发现 Aβ-PET 和 CSF tau 病理学与 AD 临床谱中的认知下降有关，两者都是痴呆进展的潜在预测因子。其中，Aβ-PET（A+T- 受试者）是 ADAS-13、ADNI-MEM 和 MMSE 评分的纵向认知下降的独立可靠预测因子，而不是 tau 病理学（A-T+ 受试者），表明 tau 积累与未来认知障碍没有密切相关，而不受 Aβ 沉积的驱动。值得注意的是，有相当比例的 APOE ε4 携带者有 Aβ 病理学（A+），表现出记忆力和学习能力差。有趣的是，当添加 APOE ε4 状态时，这种情况在 ADNI-MEM 域中不会复发。最后，在基线和纵向变化时，与葡萄糖代谢低下相关的 Aβ-PET SUVR 在 A+T- 受试者中比 A-T+ 受试者更强。
总之，没有 tau 病理学（A+T-）的 Aβ-PET 单独测量是纵向认知下降的独立可靠预测因子，但可能预测不同的痴呆进展状态。然而，没有 Aβ 病理学背景的 tau 积累（A-T+）本身不足以成为认知恶化的独立预测因子。
