Weidung Bodil, Hemmingsson Eva-Stina, Olsson Jan, Sundström Torbjörn, Blennow Kaj, Zetterberg Henrik, Ingelsson Martin, Elgh Fredrik, Lövheim Hugo
Section of Geriatrics Department of Public Health and Caring Sciences Uppsala University Uppsala Sweden.
Department of Community Medicine and Rehabilitation Geriatric Medicine Umeå University Umeå Sweden.
Alzheimers Dement (N Y). 2022 Mar 14;8(1):e12264. doi: 10.1002/trc2.12264. eCollection 2022.
Herpes simplex virus (HSV) may be involved in Alzheimer's disease (AD) pathophysiology. The antiviral valacyclovir inhibits HSV replication.
This phase-II pilot trial involved valacyclovir administration (thrice daily, 500 mg week 1, 1000 mg weeks 2-4) to persons aged ≥ 65 years with early-stage AD, anti-HSV immunoglobulin G, and apolipoprotein E ε4. Intervention safety, tolerability, feasibility, and effects on Mini-Mental State Examination (MMSE) scores and cerebrospinal fluid (CSF) biomarkers were evaluated.
Thirty-two of 33 subjects completed the trial on full dosage. Eighteen percent experienced likely intervention-related mild, temporary adverse events. CSF acyclovir concentrations were mean 5.29 ± 2.31 μmol/L. CSF total tau and neurofilament light concentrations were unchanged; MMSE score and CSF soluble triggering receptor expressed on myeloid cells 2 concentrations increased ( = .02 and .03).
Four weeks of high-dose valacyclovir treatment was safe, tolerable, and feasible in early-stage AD. Our findings may guide future trial design.
单纯疱疹病毒（HSV）可能参与阿尔茨海默病（AD）的病理生理过程。抗病毒药物伐昔洛韦可抑制HSV复制。
这项II期试点试验对年龄≥65岁、患有早期AD、抗HSV免疫球蛋白G和载脂蛋白Eε4的患者给予伐昔洛韦（第1周每日3次，每次500mg；第2 - 4周每日3次，每次1000mg）。评估干预措施的安全性、耐受性、可行性以及对简易精神状态检查表（MMSE）评分和脑脊液（CSF）生物标志物的影响。
33名受试者中有32名完成了全剂量试验。18%的受试者经历了可能与干预相关的轻度、短暂不良事件。脑脊液中阿昔洛韦浓度平均为5.29±2.31μmol/L。脑脊液总tau蛋白和神经丝轻链浓度未改变；MMSE评分以及脑脊液中髓样细胞上表达的可溶性触发受体2浓度升高（P = 0.02和0.03）。
高剂量伐昔洛韦治疗4周在早期AD患者中是安全、可耐受且可行的。我们的研究结果可能为未来的试验设计提供指导。
