University of Adelaide, School of Biological Sciences, Centre for Molecular Pathology, Adelaide, SA, Australia.
Collaborative Genomics and Translation Group, Strategic Research Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
J Alzheimers Dis. 2021;80(4):1479-1489. doi: 10.3233/JAD-201133.
The PRESENILIN genes (PSEN1, PSEN2) encoding for their respective proteins have critical roles in many aspects of Alzheimer's disease (AD) pathogenesis. The PS2V transcript of PSEN2 encodes a truncated protein and is upregulated in AD brains; however, its relevance to AD and disease progression remains to be determined.
Assess transcript levels in postmortem AD and non-AD brain tissue and in lymphocytes collected under the Australian Imaging Biomarker and Lifestyle (AIBL) study.
Full length PSEN2 and PS2V transcript levels were assessed by quantitative digital PCR in postmortem brain tissue (frontal cortex and hippocampus) from control, AD, frontotemporal dementia (FTD), and Lewy body dementia (LBD). Transcript levels were also assessed in lymphocytes obtained from the Perth subset of the AIBL study (n = 160). Linear regression analysis was used to assess correlations between transcript copy number and brain volume and neocortical amyloid load.
PS2V levels increased in AD postmortem brain but PS2V was also present at significant levels in FTD and LBD brains. PS2V transcript was detected in lymphocytes and PS2V/PSEN2 ratios were increased in mild cognitive impairment (p = 0.024) and AD (p = 0.019) groups compared to control group. Increased ratios were significantly correlated with hippocampal volumes only (n = 62, β= -0.269, p = 0.03).
Taken together, these results suggest that PS2V may be a marker of overall neurodegeneration.
编码其各自蛋白质的早老素基因（PSEN1、PSEN2）在阿尔茨海默病（AD）发病机制的许多方面都起着关键作用。PSEN2 的 PS2V 转录本编码一种截断的蛋白质，在 AD 大脑中上调；然而，其与 AD 和疾病进展的相关性仍有待确定。
评估 AD 和非 AD 脑组织以及澳大利亚成像生物标志物和生活方式（AIBL）研究中采集的淋巴细胞中的转录本水平。
通过定量数字 PCR 评估对照、AD、额颞叶痴呆（FTD）和路易体痴呆（LBD）死后脑组织（额叶皮质和海马体）中的全长 PSEN2 和 PS2V 转录本水平。还评估了 AIBL 研究珀斯子集中获得的淋巴细胞中的转录本水平（n = 160）。线性回归分析用于评估转录本拷贝数与脑容量和新皮质淀粉样蛋白负荷之间的相关性。
PS2V 水平在 AD 死后脑中增加，但在 FTD 和 LBD 脑中也存在显著水平。PS2V 转录本在淋巴细胞中检测到，并且 PS2V/PSEN2 比值在轻度认知障碍（p = 0.024）和 AD（p = 0.019）组中高于对照组。增加的比值与海马体体积显著相关（n = 62，β= -0.269，p = 0.03）。
综上所述，这些结果表明 PS2V 可能是整体神经退行性变的标志物。
