Relevance of a Truncated PRESENILIN 2 Transcript to Alzheimer's Disease and Neurodegeneration.
Background: 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 prog...
| Published in: | Journal of Alzheimer's Disease Vol. 80; no. 4; pp. 1479 - 1490 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , |
| Format: | research Journal Article |
| Published: |
Sage Publications Inc.
2021
|
| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=151820992&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 151820992 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 13872877 FLR jtl: Journal of Alzheimer's Disease issn: 13872877 maglogo: N pubinfo: dt: 2021 vid: 80 iid: 4 pid: 20732 pub: Sage Publications Inc. place: Thousand Oaks, California artinfo: ui: 151820992 151820992 NLM33720885 151820992 10.3233/JAD-201133 NLM33720885 151820992 ppf: 1479 ppct: 11 formats: tig: atl: Relevance of a Truncated PRESENILIN 2 Transcript to Alzheimer's Disease and Neurodegeneration. aug: au: Moussavi Nik, Seyyed Hani Porter, Tenielle Newman, Morgan Bartlett, Benjamin Khan, Imran Sabale, Miheer Eccles, Melissa Woodfield, Amy Groth, David Dore, Vincent Villemagne, Victor L. Masters, Colin L. Martins, Ralph N. Laws, Simon M. Lardelli, Michael Verdile, Giuseppe affil: University of Adelaide, School of Biological Sciences, Centre for Molecular Pathology, Adelaide, SA, Australia sug: subj: Lewy Body Disease Membrane Proteins Frontotemporal Dementia Alzheimer's Disease Australia Aged Disease Progression Male Brain Pathology Linear Regression Middle Age Aged, 80 and Over Female RNA Human Comparative Studies Multicenter Studies Evaluation Research Validation Studies Aged: 65+ years Middle Aged: 45-64 years Aged, 80 & over Male Female ab: Background: 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.Objective: Assess transcript levels in postmortem AD and non-AD brain tissue and in lymphocytes collected under the Australian Imaging Biomarker and Lifestyle (AIBL) study.Methods: 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.Results: 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).Conclusion: Taken together, these results suggest that PS2V may be a marker of overall neurodegeneration. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|