1. Neurogranin, a synaptic protein, is associated with memory independent of Alzheimer biomarkers
- Author
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Casaletto, Kaitlin B, Elahi, Fanny M, Bettcher, Brianne M, Neuhaus, John, Bendlin, Barbara B, Asthana, Sanjay, Johnson, Sterling C, Yaffe, Kristine, Carlsson, Cynthia, Blennow, Kaj, Zetterberg, Henrik, and Kramer, Joel H
- Subjects
Alzheimer's Disease ,Dementia ,Brain Disorders ,Aging ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Neurodegenerative ,Neurosciences ,Acquired Cognitive Impairment ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Aged ,Aged ,80 and over ,Alzheimer Disease ,Amyloid beta-Peptides ,Apolipoproteins E ,Cross-Sectional Studies ,Enzyme-Linked Immunosorbent Assay ,Female ,Hippocampus ,Humans ,Imaging ,Three-Dimensional ,Independent Living ,Magnetic Resonance Imaging ,Male ,Memory Disorders ,Mental Recall ,Middle Aged ,Neurogranin ,Neuropsychological Tests ,Peptide Fragments ,tau Proteins ,Clinical Sciences ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
ObjectiveTo determine the association between synaptic functioning as measured via neurogranin in CSF and cognition relative to established Alzheimer disease (AD) biomarkers in neurologically healthy older adults.MethodsWe analyzed CSF concentrations of neurogranin, β-amyloid (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau) among 132 neurologically normal older adults (mean 64.5, range 55-85), along with bilateral hippocampal volumes and a measure of episodic memory (Auditory Verbal Learning Test, delayed recall). Univariable analyses examined the relationship between neurogranin and the other AD-related biomarkers. Multivariable regression models examined the relationship between neurogranin and delayed recall, adjusting for age and sex, and interaction terms (neurogranin × AD biomarkers).ResultsHigher neurogranin concentrations were associated with older age (ρ = 0.20, p = 0.02), lower levels of p-tau and t-tau, and smaller hippocampal volumes (p < 0.03), but not with CSF Aβ42 (p = 0.18). In addition, CSF neurogranin demonstrated a significant relationship with memory performance independent of the AD-related biomarkers; individuals with the lowest CSF neurogranin concentrations performed better on delayed recall than those with medium or high CSF neurogranin concentrations (p < 0.01). Notably, CSF p-tau, t-tau, and Aβ42 and hippocampal volumes were not significantly associated with delayed recall scores (p > 0.40), and did not interact with neurogranin to predict memory (p > 0.10).ConclusionsSynaptic dysfunction (assessed via neurogranin) may be an early pathologic process in age-related neurodegeneration, and a sensitive marker of age-related cognitive abilities, potentially preceding or even acting independently from AD pathogenesis. Synaptic functioning may be a useful early marker of cognitive aging and possibly a target for future brain aging interventions.
- Published
- 2017