McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Department of Biomedical Physiology & Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada.
Alzheimers Dement. 2024 Sep;20(9):6316-6331. doi: 10.1002/alz.14110. Epub 2024 Jul 12.
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.
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.
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.
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.
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.
尽管平行研究表明阿尔茨海默病（AD）存在淀粉样蛋白-β 积累、皮质神经生理信号改变和多系统神经递质紊乱，但这些现象之间的关系仍不清楚。
我们使用脑磁图、正电子发射断层扫描和 19 种神经递质图谱研究了神经生理改变、淀粉样蛋白-β 沉积与皮质神经化学梯度之间的关系。
在轻度认知障碍和 AD 患者中，皮质节律的变化与胆碱能、血清素能和多巴胺能系统在拓扑上是一致的。这些一致性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，影响神经生理改变与毒蕈碱型乙酰胆碱受体的一致性。在具有无症状淀粉样蛋白-β积累的个体的独立数据集，大部分淀粉样蛋白-β-神经化学和 α 波段神经生理化学一致性得到了复制。
我们的研究结果表明，AD 病理学在拓扑上与化学神经调质系统的皮质分布一致，并与临床严重程度相关，这对潜在的药物治疗途径具有重要意义。
AD 患者皮质节律的改变是沿着神经化学边界组织的。这些一致性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一致性。大多数一致性在有临床前阿尔茨海默病病理的参与者中得到了复制。
