Relevance of a truncated PRESENILIN 2 transcript to Alzheimer's disease and neurodegeneration

Authors

Seyyed Hani Moussavi Nik
Tenielle Porter, Edith Cowan UniversityFollow
Morgan Newman
Benjamin Bartlett
Imran Khan
Miheer Sabale
Melissa Eccles
Amy Woodfield
David Groth
Vincent Dore
Victor L. Villemagne, Edith Cowan UniversityFollow
Colin L. Masters
Ralph N. Martins, Edith Cowan UniversityFollow
Simon M. Laws, Edith Cowan UniversityFollow
Michael Lardelli
Giuseppe Verdile, Edith Cowan UniversityFollow

Document Type

Journal Article

Publication Title

Journal of Alzheimer's Disease

Volume

80

Issue

4

First Page

1479

Last Page

1489

PubMed ID

33720885

Publisher

IOS Press

School

School of Medical and Health Sciences / Centre for Precision Health

RAS ID

36630

Comments

Moussavi Nik, S. H., Porter, T., Newman, M., Bartlett, B., Khan, I., Sabale, M., ... Verdile, G. (2021). Relevance of a truncated PRESENILIN 2 transcript to Alzheimer’s disease and neurodegeneration. Journal of Alzheimer's Disease, 80(4), 1479-1489. https://doi.org/10.3233/JAD-201133

Abstract

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.

DOI

10.3233/JAD-201133

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