Abstract：Leukoaraiosis is a descriptive term for rarefaction of the white matter, showing up as nonspecific changes in the periventricular and sub-cortex white matter frequently seen on CT and MRI. Currently researches focus on its risk factors, clinical manifestations, treatment, and so on. Most studies have shown that leukoaraiosis is caused by low perfusion of white matter area related to chronic ischemia. Studies also demonstrate the relationship between leukoaraiosis and certain changesof human genes and protein. In this paper, the newest genomics and proteomics researches of leukoaraiosis are reviewed.
[1] Steingart A，Hachinski VC，Lau C，et al. Cognitive and neurologic findings in demented patients with diffuse white matter lucencies on computed tomographic scan （leuko-araiosis）[J]. Jama Neurol，1987，44（1）：32-35.
[2] Bridges LR，Andoh J，Lawrence AJ，et al. Blood-brain barrier dysfunction and cerebral small vessel disease （arteriolosclerosis） in brains of older people [J]. J Neuropathol Exp Neurol，2014，73（11）：1026.
[3] Meschia JF. Ischemic stroke as a complex genetic disorder [J]. Seminars Neurol，2006，26（1）：49-56.
[4] Godin O，Tzourio C，Maillard P，et al. Apolipoprotein E genotype is related to progression of white matter lesion load [J]. Stroke，2009，40（10）：3186-3190.
[5] Bronge L，Fernaeus S E，Blomberg M，et al. White matter lesions in Alzheimer patients are influenced by apolipoprotein E genotype [J]. Dement Geriatr Cogn Disord，1999，10（2）：89.
[6] Szolnoki Z. Pathomechanism of leukoaraiosis：a molecular bridge between the genetic，biochemical，and clinical processes （a mitochondrial hypothesis）[J].Neuromolecular Medicine，2007，9（1）：21.
[7] Premkumar DR，Cohen DL，Hedera P，et al. Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease [J]. Am J Pathol，1996，148（6）：2083-2095.
[8] Hassan A，Lansbury A，Catto A J，et al. Angiotensin converting enzyme insertion/deletion genotype is associated with leukoaraiosis in lacunar syndromes [J]. J Neurol Neurosurg Psychiatry，2002，72（3）：343-346.
[9] Szolnoki Z，Somogyvári F，Kondacs A，et al. Evaluation of the roles of common genetic mutations in leukoaraiosis [J]. Acta Neurologica Scandinavica，2001，104（5）：281-287.
[10] Stankiewicz Z，Wajnert J. A homozygous genetic variant of mitochondrial uncoupling protein 4 affects the occurrence of leukoaraiosis [J]. Acta Neurologica Scandinavica，2011，123（5）：352-357.
[11] Choi JC. Genetics of cerebral small vessel disease [J]. J Stroke，2015，17（1）：7-16.
[12] Schmidt H，Zeginigg M，Wiltgen M，et al. Genetic variants of the NOTCH3 gene in the elderly and magnetic resonance imaging correlates of age-related cerebral small vessel disease[J]. Brain，2011，134（11）：3384.
[13] Richards A，Arn MJM van den Maagdenberg，Jen JC，et al. C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy [J]. Nat Genet，2007，39（9）：1068.
[14] Lanfranconi S，Markus HS. COL4A1 mutations as a monogenic cause of cerebral small vessel disease：a systematic review [J]. Stroke，2010，41（8）：513-518.
[15] Nozaki H，Nishizawa M，Onodera O. Features of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy [J]. Stroke，2014，45（11）：3447-3453.
[16] Shan XY，Chen GZ，Cheng GP，et al. Cyclooxygenase 2 genetic polymorphism may increase the risk of developing leukoaraiosis in Chinese [J]. J Mol Neurosci Mn，2013， 51（2）：461-466.
[17] Van Dijk EJ，Prins ND，Vermeer SE，et al. C-reactive protein and cerebral small-vessel disease：the Rotterdam Scan Study [J]. Circulation，2005，112（6）：900-905.
[18] Cheng X，Dong Q. Potential blood biomarkers inage-related cerebral small vessel disease [J]. Curr Geriatr Rep，2012，1（2）：76-84.
[19] Park L，Wang G，Moore J，et al. The key role of transient receptor potential melastatin-2 channels in amyloid-β-induced neurovascular dysfunction [J]. Nat Commun，2014， 5：5318.
[20] Gurol ME，Viswanathan A，Gidicsin C，et al. Cerebral amyloid angiopathy burden associated with leukoaraiosis：a PET/MRI study [J]. Ann Neurol，2013，73（4）：529-536.
[21] Brickman AM. Contemplating Alzheimer′s disease and the contribution of white matter hyperintensities [J]. Curr Neurol Neurosci Rep，2013，13（12）：1-9.
[22] Candelariojalil E，Thompson J，Taheri S，et al. Matrix metalloproteinases are associated with increased blood–brain barrier opening in vascular cognitive impairment[J]. Stroke，2011，42（5）：1345-1350.
[23] Rosenberg GA，Sullivan N，Esiri MM. White matter damage is associated with matrix metalloproteinases in vascular dementia [J]. Stroke，2001，32（5）：1162-1168.
[24] Aribisala BS，Wiseman S，Morris Z，et al. Circulating inflammatory markers are associated with magnetic resonance imaging-visible perivascular spaces but not directly with white matter hyperintensities [J]. Stroke，2014，45（2）：605-607.
[25] Fornage M，Chiang YA，O'Meara ES，et al. Biomarkers of Inflammation and MRI-defined small vessel disease of the brain：the cardiovascular health study [J]. Stroke，2008， 39（7）：1952-1959.
2017, Vol. 14 
京公网安备 11010502046598号