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Publications

Journal Article Epublish

PubMed: 40725474 DOI: 10.3390/genes16070818

Brain and CSF Alzheimer's Biomarkers Are Associated with SERPINE1 Gene Expression.

Genes (Basel) 16(7)

Authors: Cynthia Picard, Henrik Zetterberg, Kaj Blennow, Sylvia Villeneuve, Judes Poirier, On Behalf Of The Prevent-Ad Research Group

Affiliations

  • Douglas Mental Health University Institute, Montréal, QC H4H 1R3, Canada.
  • Centre for the Studies on Prevention of Alzheimer's Disease, Montréal, QC H4H 1R3, Canada.
  • Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 431 30 Mölndal, Sweden. Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, UK. UK Dementia Research Institute at UCL, London WC1E 6BT, UK. Hong Kong Center for Neurodegenerative Diseases, Hong Kong 1501-02 15, China. Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53715, USA. Centre for Brain Research, Indian Institute of Science, Bangladore 560012, India.
  • Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
  • Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 431 30 Mölndal, Sweden.
  • Department of Psychiatry, McGill University, Montréal, QC H3A 0C8, Canada.

Abstract

BACKGROUND

SERPINE1, also known as plasminogen activator inhibitor (PAI), has been proposed as a potential blood biomarker for the early detection and diagnosis of Alzheimer's disease (AD). Expanding on previous studies, this research contrasted SERPINE1 levels in CSF and brain tissue of AD patients and those at risk for AD with established AD biomarkers.

METHODS

Utilizing OLINK and immunoassay methods, CSF SERPINE1 protein levels were quantified across two separate cohorts: PREVENT-AD and ADNI. Microarray and RNAseq were used to measure tissue SERPINE1 mRNA levels in two separate cohorts: the Douglas-Bell Canada Brain Bank and the Mayo Clinic Brain Bank.

RESULTS

At the pre-clinical stage, elevated CSF levels of pTau, tTau and synaptic markers, alongside reduced hippocampal volume, correlate with CSF SERPINE1 levels. Elevated cortical SERPINE1 mRNA levels in autopsy-confirmed AD show weak correlation with regional plaques and tangles densities, but strong correlation with Braak staging.

CONCLUSIONS

CSF SERPINE1 levels can be used as an early biomarker for the detection of pathological changes associated with AD. Higher SERPINE1 levels correlate more strongly with tau pathology than with amyloid formation or deposition.

MeSH

Genes, Genomics, Brain, Biomarkers, Tissues, Gene Expression