摘要
背景：载脂蛋白（APOE）ε4等位基因是阿尔茨海默病（AD）的众所周知的危险因素，睡眠障碍通常与AD有关。然而，很少有研究调查AP中APOEε4与异常睡眠模式（N +）之间的关系。 目的：研究APOE基因型，路易体病理学和异常睡眠模式之间的关系，这是一组在尸检时评估已知AD负荷的受试者。 方法：从国家阿尔茨海默氏症协调中心数据库获得的2,368例病例数据分类如下：Braak分期V / VI和CERAD频繁神经炎斑块为高负荷AD，Braak分期III / IV和中度CERAD为中间负荷AD，Braak分期0 / I / II和不常见的CERAD为低负载AD。两项措施之间的差异被丢弃。 结果：与女性（35.1％）相比，男性（42.4％）的睡眠中断更为频繁，载体（42.3％）与ε4的非携带者（36.5％）相比更为频繁。在具有高AD负荷和路易体病理学的女性受试者中，与ε4的杂合子（ε4/ x）或非携带者相比，纯合子（ε4/ε4）携带者经常中断睡眠。这种隐性，性别特异性和路易性身体关联让人想起ε4对AD精神病的影响。然而，在调整协变量后，这种关联失去了。在AD病理无低的受试者中，女性ε4携带者的夜间紊乱明显多于非携带者;这种效应与路易体病理学的存在无关。 结论：APOEε4对睡眠障碍的影响取决于性别和AD负荷的严重程度。
关键词: 阿尔茨海默病，载脂蛋白E，睡眠行为，路易体，危险因素，神经病理学，性别。
[1]
Kim J, Basak JM, Holtzman DM. The role of apolipoprotein E in Alzheimer’s disease. Neuron 63(3): 287-03. (2009)
[2]
Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261(5123): 921-3. (1993)
[3]
Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 278(16): 1349-56. (1997)
[4]
Uchikado H, Lin WL, DeLucia MW, Dickson DW. Alzheimer disease with amygdala Lewy bodies: a distinct form of alpha-synucleinopathy. J Neuropathol Exp Neurol 65(7): 685-97. (2006)
[5]
Kotzbauer PT, Trojanowsk JQ, Lee VM. Lewy body pathology in Alzheimer’s disease. J Mol Neurosci 17(2): 225-32. (2001)
[6]
Hamilton RL. Lewy bodies in Alzheimer’s disease: a neuropathological review of 145 cases using alpha-synuclein immunohistochemistry. Brain Pathol 10(3): 378-84. (2000)
[7]
Chung EJ, Babulal GM, Monsell SE, Cairns NJ, Roe CM, Morris JC. Clinical features of alzheimer disease with and without lewy bodies. JAMA Neurol 72(7): 789-96. (2015)
[8]
Lim A, Yu L, Kowgier M, Schneider J, Buchman A, Bennett D. Modification of the relationship of the apolipoprotein e ε4 allele to the risk of alzheimer disease and neurofibrillary tangle density by sleep. JAMA Neurology 70(12): 1544. (2013)
[9]
Vitiello MV, Borson S. Sleep disturbances in patients with Alzheimer’s disease: epidemiology, pathophysiology and treatment. CNS Drugs 15(10): 777-96. (2001)
[10]
Chen DW, Wang J, Zhang LL, Wang YJ, Gao CY. Cerebrospinal fluid amyloid-β levels are increased in patients with insomnia. J Alzheimers Dis 61(2): 645-51. (2018)
[11]
Carvalho DZ, St Louis EK, Knopman DS, Boeve BF, Lowe VF, Roberts RO, et al. Association of excessive daytime sleepiness with longitudinal β-amyloid accumulation in elderly persons without dementia. JAMA Neurol 75(6): 672-80. (2018)
[12]
Sprecher KE, Koscik RL, Carlsson CM, Zetterberg H, Blennow K, Okonkwo OC, et al. Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology 89(5): 445-53. (2017)
[13]
Ju YE, Lucey BP, Holtzman DM. Sleep and Alzheimer disease pathology--a bidirectional relationship. Nat Rev Neurol 10(2): 115-9. (2013)
[14]
Farlow MR. Alzheimer’s disease: clinical implications of the apolipoprotein E genotype. Neurology 48(5)(Suppl. 6): S30-4. (1997)
[15]
Hostage CA, Roy Choudhury K, Doraiswamy PM, Petrella JR. Alzheimer’s Disease Neuroimaging I. Dissecting the gene dose-effects of the APOE epsilon4 and epsilon2 alleles on hippocampal volumes in aging and Alzheimer’s disease. PLoS One 8(2): e54483. (2013)
[16]
Spira AP, An Y, Resnick SM. Self-reported sleep and beta-amyloid deposition in older adults-reply. JAMA Neurol 71(5): 651-2. (2014)
[17]
Drogos LL, Gill SJ, Tyndall AV, Raneri JK, Parboosingh JS, Naef A, et al. Evidence of association between sleep quality and APOE epsilon4 in healthy older adults: apilot study. Neurology 87(17): 1836-42. (2016)
[18]
Kim J, Fischer CE, Schweizer TA, Munoz DG. Gender and pathology-specific effect of apolipoprotein e genotype on psychosis in Alzheimer’s disease. Curr Alzheimer Res 14(8): 834-40. (2017)
[19]
Payami H, Zareparsi S, Montee KR, Sexton GJ, Kaye JA, Bird TD, et al. Gender difference in apolipoprotein E-associated risk for familial Alzheimer disease: a possible clue to the higher incidence of Alzheimer disease in women. Am J Hum Genet 58(4): 803-11. (1996)
[20]
Altmann A, Tian L, Henderson VW, Greicius MD. Alzheimer’s Disease Neuroimaging Initiative I. Sex modifies the APOE-related risk of developing Alzheimer disease. Ann Neurol 75(4): 563-73. (2014)
[21]
Xing Y, Tang Y, Jia J. Sex differences in neuropsychiatric symptoms of Alzheimer’s disease: the modifying effect of apolipoprotein e epsilon4 status. Behav Neurol 2015: 275256. (2015)
[22]
Stern Y, Jacobs D, Goldman J, Gomez-Tortosa E, Hyman BT, Liu Y, et al. An investigation of clinical correlates of Lewy bodies in autopsy-proven Alzheimer disease. Arch Neurol 58(3): 460-5. (2001)
[23]
Yesavage JA, Friedman L, Kraemer H, Tinklenberg JR, Salehi A, Noda A, et al. Sleep/wake disruption in Alzheimer’s disease: APOE status and longitudinal course. J Geriatr Psychiatry Neurol 17(1): 20-4. (2004)
[24]
Deschenes CL, McCurry SM. Current treatments for sleep disturbances in individuals with dementia. Curr Psychiatry Rep 11(1): 20-6. (2009)
Related Books
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Frontiers in Clinical Drug Research-Dementia
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Article Metrics
45
9
1