DOI: 10.5061/dryad.vdncjsxv4
title: CSF synaptic biomarkers in the preclinical stage of Alzheimer’s disease and their association with MRI and PET markers of neurodegeneration: a cross-sectional study

description: Objective: To determine whether CSF synaptic biomarkers are altered in the
 early preclinical stage of the Alzheimer’s continuum and associated with
 Alzheimer’s disease (AD) risk factors, primary pathology, and
 neurodegeneration markers. Methods: Cross-sectional study in the ALFA+
 cohort, comprising middle-aged cognitively unimpaired participants. CSF
 neurogranin and GAP-43 were measured using immunoassays and SNAP-25 and
 synaptotagmin-1 using immunoprecipitation mass spectrometry. AD CSF
 biomarkers Aβ42/40, p-tau and t-tau, and the neurodegeneration biomarker
 NfL were also measured. Participants underwent structural MRI, and
 fluorodeoxyglucose and Aβ PET imaging. General linear modeling
 was used to test the associations between CSF synaptic biomarkers and risk
 factors, Aβ pathology, tau pathology, and neurodegeneration markers.
 Results: All CSF synaptic biomarkers increased with age. CSF neurogranin
 was higher in females, while CSF SNAP-25 was higher in APOE-ε4 carriers.
 All CSF synaptic biomarkers increased with higher Aβ load (as
 measured by CSF Aβ42/40 and Aβ PET Centiloid values) and, importantly, the
 synaptic biomarkers were increased even in individuals in the earliest
 stages of Aβ deposition. Higher CSF synaptic biomarkers were also
 associated with higher CSF p-tau and NfL. Higher CSF neurogranin and
 GAP-43 were significantly associated with higher brain metabolism, but
 lower cortical thickness in AD-related brain regions. Conclusion: CSF
 synaptic biomarkers increase in early preclinical stages of the
 Alzheimer’s continuum even when a low burden of Aβ pathology is
 present, and they differ in their association with age, sex, APOE-ε4, and
 markers of neurodegeneration.
description: The ALFA+ study includes 450 cognitively unimpaired participants
 at increased risk of Alzheimer's disease. The current dataset
 includes the 397 first consecutive participants with available
 cerebrospinal fluid biomarkers for Alzheimer's disease pathology and
 the synaptic biomarkers neurogranin, synaptotagmin-1, SNAP-25 and
 GAP-43. CSF β-amyloid (Aβ) status was defined by the
 CSF Aβ42/40 ratio, and participants were classified as CSF Aβ-positive
 (A+) if CSF Aβ42/40 &lt; 0.071. Furthermore, the following 3 groups
 based on both CSF and PET Aβ status (CSF/PET Aβ status groups) were
 defined: (1) CSF/PET Aβ-negative group (negative CSF Aβ42/40 and Aβ PET
 &lt;30 Centiloids), (2) group with low burden of Aβ pathology
 (positive CSF Aβ42/40 but Aβ PET &lt;30 Centiloids), and (3) CSF/PET
 Aβ-positive (positive CSF Aβ42/40 and Aβ PET ≥ 30 Centiloids).
description: The following variables are included in the dataset:
 <strong>Cerebrospinal fluid synaptic
 biomarkers:</strong>
  - "Neurogranin_pgml": referring to Neurogranin
 (pg/ml)  - "SYT1_pM": referring to
 Synaptotagmin-1 (pM)  - "SNAP-25_pM":
 referring to synaptosomal-associated protein- 25 (SNAP-25) (pM)
  - "GAP43_pgml": referring to growth-associated
 protein-43 (GAP-43) (pg/ml)
 <strong>Participants' classification according
 to CSF/PET Aβ status groups</strong> -
 "CSF_PET_Aβ group": referring to CSF/PET Aβ status groups, with
 3 levels: 1) "CSF-PET-": CSF/PET Aβ-negative
 group (negative CSF Aβ42/40 and Aβ PET &lt;30 Centiloids)
 2) "CSF+PET-": group with low burden of Aβ pathology
 (positive CSF Aβ42/40 but Aβ PET &lt;30 Centiloids)
 3) "CSF+PET+": positive CSF Aβ42/40 and Aβ PET ≥ 30
 Centiloids Missing values are displayed as
 "NULL".