Lukiw Walter J, Rogaev Evgeny I
Louisiana State University (LSU) Neuroscience Center, Louisiana State University Health Science CenterNew Orleans, LA, USA.
Department of Ophthalmology, Louisiana State University Health Science CenterNew Orleans, LA, USA.
Front Aging Neurosci. 2017 Apr 10;9:87. doi: 10.3389/fnagi.2017.00087. eCollection 2017.
Alzheimer's disease (AD) is a terminal, age-related neurological syndrome exhibiting progressive cognitive and memory decline, however AD patients in addition exhibit ancillary neuropsychiatric symptoms (NPSs) and these include aggression. In this communication we provide recent evidence for the mis-regulation of a small family of genes expressed in the human hippocampus that appear to be significantly involved in expression patterns common to both AD and aggression. DNA array- and mRNA transcriptome-based gene expression analysis and candidate gene association and/or genome-wide association studies (CGAS, GWAS) of aggressive attributes in humans have revealed a surprisingly small subset of six brain genes that are also strongly associated with altered gene expression patterns in AD. These genes encoded on five different chromosomes (chr) include the androgen receptor (AR; chrXq12), brain-derived neurotrophic factor (BDNF; chr11p14.1), catechol-O-methyl transferase (COMT; chr22q11.21), neuronal specific nitric oxide synthase (NOS1; chr12q24.22), dopamine beta-hydroxylase (DBH chr9q34.2) and tryptophan hydroxylase (TPH1, chr11p15.1 and TPH2, chr12q21.1). Interestingly, (i) the expression of three of these six genes (COMT, DBH, NOS1) are highly variable; (ii) three of these six genes (COMT, DBH, TPH1) are involved in DA or serotonin metabolism, biosynthesis and/or neurotransmission; and (iii) five of these six genes (AR, BDNF, COMT, DBH, NOS1) have been implicated in the development, onset and/or propagation of schizophrenia. The magnitude of the expression of genes implicated in aggressive behavior appears to be more pronounced in the later stages of AD when compared to MCI. These recent genetic data further indicate that the extent of cognitive impairment may have some bearing on the degree of aggression which accompanies the AD phenotype.
阿尔茨海默病（AD）是一种晚期、与年龄相关的神经综合征，表现为进行性认知和记忆衰退，然而AD患者还会出现辅助性神经精神症状（NPSs），其中包括攻击性。在本交流中，我们提供了近期证据，表明人类海马体中一小类基因表达失调，这些基因似乎与AD和攻击性共有的表达模式密切相关。基于DNA阵列和mRNA转录组的基因表达分析以及人类攻击性特征的候选基因关联和/或全基因组关联研究（CGAS、GWAS）揭示了一个令人惊讶的小基因子集，其中六个脑基因也与AD中改变的基因表达模式密切相关。这些位于五条不同染色体（chr）上编码的基因包括雄激素受体（AR；chrXq12）、脑源性神经营养因子（BDNF；chr11p14.1）、儿茶酚-O-甲基转移酶（COMT；chr22q11.21）、神经元型一氧化氮合酶（NOS1；chr12q24.22）、多巴胺β-羟化酶（DBH chr9q34.2）和色氨酸羟化酶（TPH1，chr11p15.1和TPH2，chr12q21.1）。有趣的是，（i）这六个基因中的三个（COMT、DBH、NOS1）的表达高度可变；（ii）这六个基因中的三个（COMT、DBH、TPH1）参与多巴胺或5-羟色胺的代谢、生物合成和/或神经传递；（iii）这六个基因中的五个（AR、BDNF、COMT、DBH、NOS1）与精神分裂症的发生、发作和/或传播有关。与轻度认知障碍（MCI）相比，与攻击行为相关的基因表达程度在AD后期似乎更为明显。这些最新的遗传学数据进一步表明，认知障碍的程度可能与伴随AD表型的攻击程度有关。
