Abstract：
BACKGROUND: Despite parallel research indicating amyloid-β accumulation, alterations in cortical neurophysiological signaling, and multi-system neurotransmitter disruptions in Alzheimer\'s disease (AD), the relationships between these phenomena remains unclear.
METHODS: Using magnetoencephalography, positron emission tomography, and an atlas of 19 neurotransmitters, we studied the alignment between neurophysiological alterations, amyloid-β deposition, and the neurochemical gradients of the cortex.
RESULTS: In patients with mild cognitive impairment and AD, changes in cortical rhythms were topographically aligned with cholinergic, serotonergic, and dopaminergic systems. These alignments correlated with the severity of clinical impairments. Additionally, cortical amyloid-β plaques were preferentially deposited along neurochemical boundaries, influencing how neurophysiological alterations align with muscarinic acetylcholine receptors. Most of the amyloid-β-neurochemical and alpha-band neuro-physio-chemical alignments replicated in an independent dataset of individuals with asymptomatic amyloid-β accumulation.
CONCLUSIONS: Our findings demonstrate that AD pathology aligns topographically with the cortical distribution of chemical neuromodulator systems and scales with clinical severity, with implications for potential pharmacotherapeutic pathways.
CONCLUSIONS: Changes in cortical rhythms in Alzheimer\'s are organized along neurochemical boundaries. The strength of these alignments is related to clinical symptom severity. Deposition of amyloid-β (Aβ) is aligned with similar neurotransmitter systems. Aβ deposition mediates the alignment of beta rhythms with cholinergic systems. Most alignments replicate in participants with pre-clinical Alzheimer\'s pathology.
METHODS: Using magnetoencephalography, positron emission tomography, and an atlas of 19 neurotransmitters, we studied the alignment between neurophysiological alterations, amyloid-β deposition, and the neurochemical gradients of the cortex.
RESULTS: In patients with mild cognitive impairment and AD, changes in cortical rhythms were topographically aligned with cholinergic, serotonergic, and dopaminergic systems. These alignments correlated with the severity of clinical impairments. Additionally, cortical amyloid-β plaques were preferentially deposited along neurochemical boundaries, influencing how neurophysiological alterations align with muscarinic acetylcholine receptors. Most of the amyloid-β-neurochemical and alpha-band neuro-physio-chemical alignments replicated in an independent dataset of individuals with asymptomatic amyloid-β accumulation.
CONCLUSIONS: Our findings demonstrate that AD pathology aligns topographically with the cortical distribution of chemical neuromodulator systems and scales with clinical severity, with implications for potential pharmacotherapeutic pathways.
CONCLUSIONS: Changes in cortical rhythms in Alzheimer\'s are organized along neurochemical boundaries. The strength of these alignments is related to clinical symptom severity. Deposition of amyloid-β (Aβ) is aligned with similar neurotransmitter systems. Aβ deposition mediates the alignment of beta rhythms with cholinergic systems. Most alignments replicate in participants with pre-clinical Alzheimer\'s pathology.
摘要：
背景：尽管平行研究表明淀粉样蛋白-β积累，皮质神经生理信号的改变，和阿尔茨海默病（AD）中的多系统神经递质破坏，这些现象之间的关系仍然不清楚。
方法：使用脑磁图，正电子发射断层扫描，和19种神经递质的地图集，我们研究了神经生理学改变之间的排列，淀粉样β沉积，和皮质的神经化学梯度。
结果：在轻度认知障碍和AD患者中，皮质节律的变化在地形学上与胆碱能，血清素能,和多巴胺能系统。这些排列与临床损伤的严重程度相关。此外,皮质淀粉样蛋白-β斑块优先沿神经化学边界沉积，影响神经生理学改变与毒蕈碱乙酰胆碱受体的关系。大多数淀粉样蛋白-β-神经化学和α-带神经生理化学比对在无症状淀粉样蛋白-β积累的个体的独立数据集中复制。
结论：我们的研究结果表明，AD病理与化学神经调质系统的皮质分布在地形图上一致，并随临床严重程度而变化。对潜在的药物治疗途径有影响。
结论：阿尔茨海默病患者皮质节律的变化是沿着神经化学边界组织的。这些排列的强度与临床症状严重程度有关。淀粉样蛋白-β(Aβ)的沉积与类似的神经递质系统一致。Aβ沉积介导β节律与胆碱能系统的排列。大多数比对在具有临床前阿尔茨海默病病理学的参与者中复制。
方法：使用脑磁图，正电子发射断层扫描，和19种神经递质的地图集，我们研究了神经生理学改变之间的排列，淀粉样β沉积，和皮质的神经化学梯度。
结果：在轻度认知障碍和AD患者中，皮质节律的变化在地形学上与胆碱能，血清素能,和多巴胺能系统。这些排列与临床损伤的严重程度相关。此外,皮质淀粉样蛋白-β斑块优先沿神经化学边界沉积，影响神经生理学改变与毒蕈碱乙酰胆碱受体的关系。大多数淀粉样蛋白-β-神经化学和α-带神经生理化学比对在无症状淀粉样蛋白-β积累的个体的独立数据集中复制。
结论：我们的研究结果表明，AD病理与化学神经调质系统的皮质分布在地形图上一致，并随临床严重程度而变化。对潜在的药物治疗途径有影响。
结论：阿尔茨海默病患者皮质节律的变化是沿着神经化学边界组织的。这些排列的强度与临床症状严重程度有关。淀粉样蛋白-β(Aβ)的沉积与类似的神经递质系统一致。Aβ沉积介导β节律与胆碱能系统的排列。大多数比对在具有临床前阿尔茨海默病病理学的参与者中复制。
