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Cerebrospinal fluid proteomic profiling of individuals with mild cognitive impairment and suspected non‐Alzheimer's disease pathophysiology
Author(s) -
Delvenne Aurore,
Gobom Johan,
Tijms Betty,
Bos Isabelle,
Reus Lianne M.,
Dobricic Valerija,
Kate Mara ten,
Verhey Frans,
Ramakers Inez,
Scheltens Philip,
Teunissen Charlotte E.,
Vandenberghe Rik,
Schaeverbeke Jolien,
Gabel Silvy,
Popp Julius,
Peyratout Gwendoline,
MartinezLage Pablo,
Tainta Mikel,
Tsolaki Magda,
FreundLevi Yvonne,
Lovestone Simon,
Streffer Johannes,
Barkhof Frederik,
Bertram Lars,
Blennow Kaj,
Zetterberg Henrik,
Visser Pieter Jelle,
Vos Stephanie J. B.
Publication year - 2023
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12713
Subject(s) - pathophysiology , cerebrospinal fluid , snap , amyloidosis , biomarker , choroid plexus , proteomics , medicine , cognitive impairment , alzheimer's disease , pathology , disease , central nervous system , biology , gene , biochemistry , computer science , computer graphics (images)
Background Suspected non‐Alzheimer's disease pathophysiology (SNAP) is a biomarker concept that encompasses individuals with neuronal injury but without amyloidosis. We aim to investigate the pathophysiology of SNAP, defined as abnormal tau without amyloidosis, in individuals with mild cognitive impairment (MCI) by cerebrospinal fluid (CSF) proteomics. Methods Individuals were classified based on CSF amyloid beta (Aβ)1‐42 (A) and phosphorylated tau (T), as cognitively normal A—T– (CN), MCI A–T+ (MCI‐SNAP), and MCI A+T+ (MCI‐AD). Proteomics analyses, Gene Ontology (GO), brain cell expression, and gene expression analyses in brain regions of interest were performed. Results A total of 96 proteins were decreased in MCI‐SNAP compared to CN and MCI‐AD. These proteins were enriched for extracellular matrix (ECM), hemostasis, immune system, protein processing/degradation, lipids, and synapse. Fifty‐one percent were enriched for expression in the choroid plexus. Conclusion The pathophysiology of MCI‐SNAP (A–T+) is distinct from that of MCI‐AD. Our findings highlight the need for a different treatment in MCI‐SNAP compared to MCI‐AD.