Gamma Induction for Amyloid Clearance in Alzheimer's Disease

伽马诱导清除阿尔茨海默病中的淀粉样蛋白

• 批准号: 10617969
• 负责人: Emiliano Santarnecchi
• 金额: $ 22.42万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10617969
• 关键词: Abeta clearance; Administrative Supplement; Affect; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease patient; Amyloid; Amyloid beta-Protein; Animal Model; Animals; Award; Behavioral; Biophysics; Brain; Cerebellum; Cerebrum; Clinical; Clinical Trials; Cognition; Cognitive deficits; Data Collection; Dementia; Deposition; Devices; Diffuse; Dose; Elderly; Electrodes; Electroencephalography; Frequencies; Goals; Guidelines; Human; Impaired cognition; Individual; Inflammatory; Interneurons; Intervention; Investigation; Lead; Life Expectancy; Link; Literature; Longevity; Magnetic Resonance Imaging; Measures; Medicine; Memory; Microglia; Monitor; Mus; Nature; Nerve Degeneration; Neurobiology; Neurodegenerative Disorders; Neurofibrillary Tangles; Neuronavigation; Parents; Participant; Pathogenesis; Pathologic; Patients; Periodicity; Play; Population; Positron-Emission Tomography; Process; Proteins; Protocols documentation; Public Health; Randomized; Resolution; Risk Factors; Role; Safety; Seminal; Senile Plaques; Societies; Structure; Time; Transcranial magnetic stimulation; Translations; United States; Update; Work; attenuation; biophysical model; brain tissue; clinically relevant; cognitive change; cognitive function; cognitive testing; electric field; experience; follow-up; human subject; improved; in vivo; mouse model; neuroinflammation; neuroregulation; novel; novel therapeutic intervention; pre-clinical; prevent; research clinical testing; response; side effect; tau-1; β-amyloid burden

Project Summary Thanks to advances in public health and medicine, the life expectancy of the world population continues to lengthen. While longer lifespan is a unique opportunity for society to benefit from the wisdom and experience of the elderly, aging is however also the greatest risk factor for neurodegenerative disorders such as Alzheimer’s disease (AD). A fundamental neurobiological substrate of cognitive decline and neurodegeneration associated with AD appears to involve alteration of neuroinflammatory processes and inhibitory interneurons’ activity associated with deposition of aberrant proteins, such as amyloid-β (Aβ) and phosphorylated tau (p-tau). Recent pre-clinical work from MIT’s Li-Huei Tsai, Ed Boyden and collaborators reveals that induction of gamma oscillations in mice can modulate activity of microglia, modify inflammatory brain processes, and lead to clearance of Aβ and p-tau deposition. Translation of such findings to humans could have transformative impact. In recent years, transcranial Alternating Current Stimulation (tACS) has been shown effective in modulating brain activity and cortical rhythmic activity by means of low-amplitude alternating (sinusoidal) currents applied transcranially. In humans, a growing body of literature has shown how tACS can be applied safely if appropriate guidelines are followed, and that when applied at the appropriate alternating frequency it is possible to entrain gamma oscillations for up to 70 minutes after the end of a single stimulation session and enhance cognition. Furthermore, repeated sessions of tACS on consecutive days are safe and lead to an additive effect with longer lasting neuromodulatory impact on brain oscillation. Given the potential for gamma entrainment in humans via tACS, the parent R01 award issued in 2018 is supporting a clinical trial investigating the impact of tACS on gamma oscillatory activity, as well as its effect on Aβ and p-tau clearance and cognition. The present administrative supplement will support the upgrade of our originally proposed solutions for monitoring of gamma activity, via an improved electroencephalography device, a transcranial magnetic stimulation platform for investigation of inhibitory and excitatory cortical circuitry, and a neuronavigation suite for accurate tracking of the biophysical impact of tACS on brain structures.

项目概要 由于公共卫生和医学的进步，世界人口的预期寿命 继续拉长。虽然更长的寿命是社会受益的独特机会 凭借老年人的智慧和经验，衰老也是最大的风险因素 神经退行性疾病，例如阿尔茨海默病 (AD)。基础神经生物学 与 AD 相关的认知能力下降和神经变性的基础似乎涉及 神经炎症过程和抑制性中间神经元活动的改变与 异常蛋白质的沉积，例如淀粉样蛋白-β (Aβ) 和磷酸化 tau (p-tau)。最近的 麻省理工学院的 Li-Huei Tsai、Ed Boyden 及其合作者的临床前工作表明，诱导 小鼠的伽马振荡可以调节小胶质细胞的活动，改变炎症性大脑 过程，并导致 Aβ 和 p-tau 沉积的清除。将这些发现转化为 人类可以产生变革性的影响。近年来，经颅交流电 刺激 (tACS) 已被证明可以有效调节大脑活动和皮质节律 通过经颅施加低幅度交流（正弦）电流来进行活动。在 人类，越来越多的文献表明，在适当的情况下如何安全地应用 tACS 遵循指导方针，并且当以适当的交流频率应用时，它是 单次刺激结束后，可能会产生长达 70 分钟的伽马振荡 会议并增强认知。此外，连续几天重复进行 tACS 治疗 是安全的，并且会产生附加效应，对大脑产生更持久的神经调节影响 振荡。鉴于通过 tACS 可能在人体中夹带伽马射线，母公司 R01 奖 2018 年发布的支持一项临床试验，调查 tACS 对伽马振荡的影响 活性及其对 Aβ 和 p-tau 清除和认知的影响。现行行政 补充将支持我们最初提出的监控解决方案的升级 通过改进的脑电图设备、经颅磁 用于研究抑制性和兴奋性皮层回路的刺激平台，以及 神经导航套件，用于准确跟踪 tACS 对大脑结构的生物物理影响。