Synaptic biomarkers in CSF aid in diagnosis, correlate with cognition and predict progression in MCI and Alzheimer's disease

Authors:
  • A(Alzheimer'S Disease Neuroimaging Initiative (Adni)
    Alzheimer'S Disease Neuroimaging Initiative (Adni)
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Abstract
Introduction: Amyloid, Tau, and neurodegeneration biomarkers can stage Alzheimer's Disease (AD). Synaptic biomarkers may help track cognition. Methods: In cognitively normal controls, Mild Cognitive Impairment (MCI) and AD, we investigated CSF biomarkers in relation to cognitive measures and as predictors of cognitive and global decline. Results: There were 90 normal controls (mean age 73.0, 58% women), 57 MCI (mean age 74.3, 35% women), and 46 AD (mean age 70.7, 41% women). CSF Aβ1‐42 and Neuronal Pentraxin 2 (NPTX2) were decreased, and CSF Tau, neurogranin, and SNAP25 increased in AD versus controls. Aβ1‐42/Tau or NPTX2/Tau discriminated AD and controls best. NPTX2/Tau correlated strongly with cognition in AD and MCI and predicted a 2–3‐year decline. We replicated findings in the ADNI cohort. Discussion: CSF synaptic biomarkers, particularly NPTX2, which regulates synaptic homeostasis, relate to cognition and predict progression in AD beyond Aβ1‐42 and Tau. This is relevant for prognosis and clinical trials.
Funding Information
  • National Institutes of Health (AGO5131)
  • Alzheimer's Drug Discovery Foundation
  • Agentschap Innoveren en Ondernemen (140105)
  • Alzheimer's Disease Neuroimaging Initiative
  • National Institutes of Health (U01 AG024904)
  • U.S. Department of War (W81XWH‐12‐2‐0012)
  • National Institute on Aging
  • National Institute of Biomedical Imaging and Bioengineering
  • AbbVie
  • Alzheimer's Association
  • Alzheimer's Drug Discovery Foundation
  • BioClinica
  • Biogen
  • Bristol-Myers Squibb
  • Eli Lilly and Company
  • Roche
  • Genentech
  • Fujirebio US
  • GE Healthcare
  • H. Lundbeck A/S
  • Merck
  • Novartis Pharmaceuticals Corporation
  • Pfizer
  • Servier
  • Takeda Pharmaceutical Company
  • Foundation for the National Institutes of Health
  • National Institutes of Health

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