Abstract To date, we still lack disease-modifying thera- pies for Alzheimer＇s disease （AD）. Here, we report that long-term administration of benfotiamine improved the cognitive ability of patients with AD. Five patients with mild to moderate AD received oral benfotiamine （300 mg daily） over 18 months. All patients were examined by positron emission tomography with Pittsburgh compound B （PiB-PET） and exhibited positive imaging with β- amyloid deposition, and three received PiB-PET imaging at follow-up. The five patients exhibited cognitive improve- ment as assayed by the Mini-Mental Status Examination （MMSE） with an average increase of 3.2 points at month 18 of benfotiamine administration. The three patients who received follow-up PiB-PET had a 36.7% increase in the average standardized uptake value ratio in the brain com- pared with that in the first scan. Importantly, the MMSE scores of these three had an average increase of 3 points during the same period. Benfotiamine significantly improved the cognitive abilities of mild to moderate AD patients independently of brain amyloid accumulation. Ourstudy provides new insight to the development of disease- modifying therapy.
Late-onset Alzheimer＇s disease （LOAD） is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.
Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons （lipids, proteins, and nucleic acids） can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, inflammation, and β-amyloid （Aβ） peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.
