Resting-state functional connectivity is associated with cerebrospinal fluid levels of the synaptic protein NPTX2 in non-demented older adults

BIOCARD Research Team

Research output: Contribution to journalArticle

Abstract

Intrinsic functional connectivity of large-scale brain networks has been shown to change with aging and Alzheimer's disease (AD). These alterations are thought to reflect changes in synaptic function, but the underlying biological mechanisms are poorly understood. This study examined whether Neuronal Pentraxin 2 (NPTX2), a synaptic protein that mediates homeostatic strengthening of inhibitory circuits to control cortical excitability, is associated with functional connectivity as measured by resting-state functional magnetic resonance imaging (rsfMRI) in five large-scale cognitive brain networks. In this cross-sectional study, rsfMRI scans were obtained from 130 older individuals (mean age = 69 years) with normal cognition (N = 113) and Mild Cognitive Impairment (N = 17); NPTX2 was measured in the same individuals in cerebrospinal fluid (CSF). Higher levels of NPTX2 in CSF were associated with greater functional connectivity in the salience/ventral attention network, based on linear regression analysis. Moreover, this association was stronger among individuals with lower levels of cognitive reserve, as measured by a composite score (comprised of years of education, reading, and vocabulary measures). Additionally, higher connectivity in the salience/ventral attention network was related to better performance on a composite measure of executive function. Levels of NPTX2 were not associated with connectivity in other networks (executive control, limbic, dorsal attention, and default-mode). Findings also confirmed prior reports that individuals with MCI have lower levels of NPTX2 compared to those with normal cognition. Taken together, the results suggest that NPTX2 mechanisms may play a central role among older individuals in connectivity within the salience/ventral attention network and for cognitive tasks that require modulation of attention and response selection.

Original languageEnglish (US)
Article number132
JournalFrontiers in Aging Neuroscience
Volume11
Issue numberJUN
DOIs
StatePublished - Jan 1 2019

Fingerprint

Cerebrospinal Fluid
Proteins
Executive Function
Cognition
Cognitive Reserve
Magnetic Resonance Imaging
Vocabulary
Brain
neuronal pentraxin
Reading
Linear Models
Alzheimer Disease
Cross-Sectional Studies
Regression Analysis
Education

Keywords

  • Cerebrospinal fluid
  • Magnetic resonance imaging
  • NPTX2
  • Resting-state functional connectivity
  • Synaptic function

ASJC Scopus subject areas

  • Aging
  • Cognitive Neuroscience

Cite this

Resting-state functional connectivity is associated with cerebrospinal fluid levels of the synaptic protein NPTX2 in non-demented older adults. / BIOCARD Research Team.

In: Frontiers in Aging Neuroscience, Vol. 11, No. JUN, 132, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Intrinsic functional connectivity of large-scale brain networks has been shown to change with aging and Alzheimer's disease (AD). These alterations are thought to reflect changes in synaptic function, but the underlying biological mechanisms are poorly understood. This study examined whether Neuronal Pentraxin 2 (NPTX2), a synaptic protein that mediates homeostatic strengthening of inhibitory circuits to control cortical excitability, is associated with functional connectivity as measured by resting-state functional magnetic resonance imaging (rsfMRI) in five large-scale cognitive brain networks. In this cross-sectional study, rsfMRI scans were obtained from 130 older individuals (mean age = 69 years) with normal cognition (N = 113) and Mild Cognitive Impairment (N = 17); NPTX2 was measured in the same individuals in cerebrospinal fluid (CSF). Higher levels of NPTX2 in CSF were associated with greater functional connectivity in the salience/ventral attention network, based on linear regression analysis. Moreover, this association was stronger among individuals with lower levels of cognitive reserve, as measured by a composite score (comprised of years of education, reading, and vocabulary measures). Additionally, higher connectivity in the salience/ventral attention network was related to better performance on a composite measure of executive function. Levels of NPTX2 were not associated with connectivity in other networks (executive control, limbic, dorsal attention, and default-mode). Findings also confirmed prior reports that individuals with MCI have lower levels of NPTX2 compared to those with normal cognition. Taken together, the results suggest that NPTX2 mechanisms may play a central role among older individuals in connectivity within the salience/ventral attention network and for cognitive tasks that require modulation of attention and response selection.",
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AU - Walker, Keenan

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AU - Lu, Hanzhang

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