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- W2898036358 abstract "Previous studies from our lab and others have shown that cerebrospinal fluid (CSF) levels of the presynaptic protein synaptosomal associated protein-25 (SNAP-25) and the post-synaptic protein neurogranin (Ng) are elevated in symptomatic Alzheimer disease (AD). We examined CSF SNAP-25 and Ng levels in a cohort of cognitively normal individuals as a function of amyloid Positron Emission Tomography (PET) status and the presence of an APOE ε4 allele. 213 volunteers from the Washington University Knight Alzheimer's Disease Research Center were included who were rated as cognitively normal and underwent clinical assessment and lumbar puncture within one year of amyloid PET. Participants were an average of 65 years old. 71 individuals carried at least one APOE ε4 allele, and 142were APOE ε4 non-carriers. Predefined cut-offs for amyloid PET-positivity were standardized uptake value ratios (SUVR) >1.219 for Florbetapir and >1.42 for Pittsburgh Compound B (PiB). SNAP-25 and Ng were measured using the Erenna platform. Analysis of covariance was implemented in SAS with PROC GLM to test the association between CSF SNAP-25 or NG and APOE ε4 status and amyloid PET positivity, while controlling for age, gender, and educational level. Amyloid PET-positive individuals had higher CSF SNAP-25 levels (covariate adjusted mean of 6.22 pg/ml versus 5.28 pg/ml, p=0.001). However, an even larger effect size was observed as a function of carrying one of more APOE ε4 allele (covariate adjusted mean of 6.70 pg/ml versus 5.28 pg/ml, p<0.0001). The robust increase in SNAP-25 levels associated with carrying an APOE ε4 allele was observed even in amyloid PET-negative individuals (p<0.0001). In contrast, while amyloid PET-positive individuals had higher Ng levels (covariate adjusted mean of 2,586 pg/ml versus 1,877 pg/ml), APOE ε4 status had no effect on Ng levels. The presynaptic CSF biomarker SNAP-25 is markedly elevated in APOE ε4 carriers. However, APOE ε4 status does not affect levels of Ng, a post-synaptic marker. It is unclear why SNAP-25 levels are increased even in APOE ε4 carriers who are amyloid PET-negative. We hypothesize that APOE ε4 may directly affect pre-synaptic integrity, even prior to the onset of amyloid deposition. Further work is needed to explore this hypothesis." @default.
- W2898036358 created "2018-10-26" @default.
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- W2898036358 date "2018-07-01" @default.
- W2898036358 modified "2023-10-16" @default.
- W2898036358 title "P4‐275: THE EMERGING CEREBROSPINAL FLUID BIOMARKER SNAP‐25 IS ELEVATED IN APOEε4 CARRIERS IN COGNITIVELY NORMAL INDIVIDUALS" @default.
- W2898036358 doi "https://doi.org/10.1016/j.jalz.2018.07.097" @default.
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