CSF synapse marker changes in predementia Alzheimer´s Disease: AMPA receptor modulators NPTX2 and NPTXR mediate cognition within A/T/N stages

Background Synapse pathology has been linked to excitotoxicity and glutamate receptor dysregulation (such as AMPAR) in Alzheimer´s Disease (AD) progression. Of the core cerebrospinal fluid (CSF) AD biomarkers for amyloid, tau pathology and neurodegeneration (A/T/N), T/N status is proposed to reflect...

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Published in:Alzheimer's & dementia 2023-12, Vol.19 (S14), p.n/a
Main Authors: Kirsebom, Bjørn‐Eivind, Nilsson, Johanna, Vromen, Eleonora M., Jarholm, Jonas Alexander, Tecelao, Sandra, Selnes, Per, Aarsland, Dag, Grøntvedt, Gøril Rolfseng, Rongve, Arvid, Skogseth, Ragnhild E, Visser, Pieter Jelle, Brinkmalm, Ann, Blennow, Kaj, Fladby, Tormod
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Language:English
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Summary:Background Synapse pathology has been linked to excitotoxicity and glutamate receptor dysregulation (such as AMPAR) in Alzheimer´s Disease (AD) progression. Of the core cerebrospinal fluid (CSF) AD biomarkers for amyloid, tau pathology and neurodegeneration (A/T/N), T/N status is proposed to reflect levels of neuronal plasticity, but fluid biomarkers for precision interventions in subgroups with increased excitotoxicity are lacking. Herein, we assess group differences of 19 CSF synapse markers including the AMPAR‐modulating NPTX, in both cognitively normal (CN) and Mild Cognitive Impairment (MCI) with either A+/T‐/N‐ and A+/T or N+ (A+/T/N+) as compared to CN A‐/T‐/N‐ and assess relationships with verbal memory recall and hippocampal volume. Methods A/T/N was determined using the CSF Aβ42/40 ratio, p‐tau181 and total‐tau in predementia AD cases (n = 194) and CN participants with normal AD biomarkers (n = 145) in the Dementia Disease Initiation cohort. CSF synapse marker concentrations were determined using mass‐spectrometry (table 1) and ELISA for GAP‐43. Adjusted for age and sex, we compared marker concentrations between CN cases (A+/T‐/N‐ n = 20; A+/T/N+ n = 40) and MCI cases (A+/T‐/N‐ n = 25;A+/T/N+ n = 109) with CN A‐/T‐/N‐ (n = 145) as the reference group. Associations to verbal memory recall and brain imaging were performed in the total sample and respective A/T/N groups adjusted for covariates. Results p
ISSN:1552-5260
1552-5279
DOI:10.1002/alz.079670