Imaging beta-amyloid in middle age alcoholics as a mechanism that increases their risk for Alzheimer’s disease

中年酗酒者中的β-淀粉样蛋白是一种增加其患阿尔茨海默病风险的机制

• 批准号: 9718353
• 负责人: RAJESH NARENDRAN
• 金额: $ 33.67万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9718353
• 关键词: Abeta synthesis; Adult; Age-Years; Alcohol abuse; Alcohol consumption; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Autopsy; C-terminal; Data; Dementia; Development; Disease; Drug abuse; Enzymes; General Population; Heavy Drinking; Human; Image; Impaired cognition; Individual; Link; Medical; Nature; Neurocognitive Deficit; Patients; Positron-Emission Tomography; Proteins; Reporting; Risk; Risk Factors; Rodent; Senile Plaques; Thiamine Deficiency; Universities; Wernicke Encephalopathy; Wernicke-Korsakoff Syndrome; Woman; alcohol use disorder; beta secretase; cognitive function; epidemiologic data; epidemiology study; hazard; human old age (65+); imaging agent; in vivo; middle age; nicastrin protein; problem drinker; radiotracer; synuclein

There is a long-established relationship between alcohol use disorders, cognitive impairments, and the development of dementia. Studies have shown that heavy alcohol use in middle aged individuals impairs cognitive function even in patients who are not diagnosed with dementia (Giovanni Piumatti, 2018; Katherine Stavro, 2012). Traditionally, the study of neurocognitive impairments in alcoholics have focused on thiamine deficiency resulting in Wernicke encephalopathy or Wernicke-Korsakoff syndrome. More recently, evidence has begun to arise linking alcohol use disorders with other types of dementia including Alzheimer’s disease. Recent epidemiological data suggests that the hazard ratio to develop Alzheimer’s disease is 2-fold greater amongst individuals with alcohol use disorders compared to the general population (Michael Schwarsinger, 2018). This relationship is especially strong when alcohol abuse is examined as a risk factor for the onset of dementia in women and middle-aged adults. These epidemiological data suggest that the ‘at risk’ period to develop dementia is shifted to the middle-age years in individuals with alcohol use disorder. Consistent with this notion alcohol consuming rodents relative to controls show an increase in the expression of several proteins (such as b-amyloid precursor protein, C-terminal fragment-b, enzyme b-secretase 1, immature nicastrin, etc.,) that are involved in the synthesis of beta-amyloid plaques (Ab). However, the only post-mortem study that examined this issue in humans found no significant increase in the aggregation of Ab, hyperphosphorylated 𝜏, or 𝛼-synuclein in alcoholics compared to controls (Leena Aho, 2009). Given the retrospective nature of postmortem studies and the fact it cannot exclude co- morbid medical, psychiatric, and drug abuse disorders, it is difficult to interpret these data. There is a great need for in vivo studies to further investigate the relationship between alcohol use disorders, Ab, and Alzheimer’s disease. The positron emission tomography (PET) radiotracer [11C]PiB, which was discovered at the University of Pittsburgh is one of the most widely used and well validated Ab imaging agents (Klunk et al., 2004). Here, we propose to use [11C]PiB and PET to contrast the rate (%) of Ab positivity (+) in 40-65 year old alcoholics and controls. We hypothesize increased Ab+ in alcoholics compared to controls. Such a finding would suggest an increased risk of Ab+, and by extension explain the increased rates of Alzheimer’s dementia in alcoholics reported in recent epidemiological studies.

长期以来，酒精使用障碍与认知障碍之间存在联系