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Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults

Vidal-Piñeiro, Didac ; Sørensen, Øystein ; Blennow, Kaj LU ; Capogna, Elettra ; Halaas, Nathalie Bodd ; Idland, Ane Victoria ; Mowinckel, Athanasia Monica ; Pereira, Joana Braga LU ; Watne, Leiv Otto and Zetterberg, Henrik LU , et al. (2022) In Neurobiology of Aging 116. p.80-91
Abstract

It is unclear whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration predict brain atrophy in cognitively healthy older adults, whether these associations can be explained by phosphorylated tau181 (p-tau) and the 42 amino acid form of amyloid-β (Aβ42) biomarkers, and which neural substrates may drive these associations. We addressed these questions in 2 samples of cognitively healthy older adults who underwent longitudinal structural MRI up to 7 years and had baseline CSF levels of heart-type fatty-acid binding protein (FABP3)=, total-tau, neurogranin, and neurofilament light (NFL) (n = 189, scans = 721). The results showed that NFL, total-tau, and FABP3 predicted entorhinal thinning and hippocampal atrophy. Brain atrophy was... (More)

It is unclear whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration predict brain atrophy in cognitively healthy older adults, whether these associations can be explained by phosphorylated tau181 (p-tau) and the 42 amino acid form of amyloid-β (Aβ42) biomarkers, and which neural substrates may drive these associations. We addressed these questions in 2 samples of cognitively healthy older adults who underwent longitudinal structural MRI up to 7 years and had baseline CSF levels of heart-type fatty-acid binding protein (FABP3)=, total-tau, neurogranin, and neurofilament light (NFL) (n = 189, scans = 721). The results showed that NFL, total-tau, and FABP3 predicted entorhinal thinning and hippocampal atrophy. Brain atrophy was not moderated by Aβ42 and the associations between NFL and FABP3 with brain atrophy were independent of p-tau. The spatial pattern of cortical atrophy associated with the biomarkers overlapped with neurogenetic profiles associated with expression in the axonal (total-tau, NFL) and dendritic (neurogranin) components. CSF biomarkers of neurodegeneration are useful for predicting specific features of brain atrophy in older adults, independently of amyloid and tau pathology biomarkers.

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@article{faf1978f-7e4e-4a9f-a420-92018827793f,
  abstract     = {{<p>It is unclear whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration predict brain atrophy in cognitively healthy older adults, whether these associations can be explained by phosphorylated tau181 (p-tau) and the 42 amino acid form of amyloid-β (Aβ42) biomarkers, and which neural substrates may drive these associations. We addressed these questions in 2 samples of cognitively healthy older adults who underwent longitudinal structural MRI up to 7 years and had baseline CSF levels of heart-type fatty-acid binding protein (FABP3)=, total-tau, neurogranin, and neurofilament light (NFL) (n = 189, scans = 721). The results showed that NFL, total-tau, and FABP3 predicted entorhinal thinning and hippocampal atrophy. Brain atrophy was not moderated by Aβ42 and the associations between NFL and FABP3 with brain atrophy were independent of p-tau. The spatial pattern of cortical atrophy associated with the biomarkers overlapped with neurogenetic profiles associated with expression in the axonal (total-tau, NFL) and dendritic (neurogranin) components. CSF biomarkers of neurodegeneration are useful for predicting specific features of brain atrophy in older adults, independently of amyloid and tau pathology biomarkers.</p>}},
  author       = {{Vidal-Piñeiro, Didac and Sørensen, Øystein and Blennow, Kaj and Capogna, Elettra and Halaas, Nathalie Bodd and Idland, Ane Victoria and Mowinckel, Athanasia Monica and Pereira, Joana Braga and Watne, Leiv Otto and Zetterberg, Henrik and Walhovd, Kristine Beate and Fjell, Anders Martin}},
  issn         = {{0197-4580}},
  keywords     = {{Cognitively healthy older adults; CSF; FABP3; Neurodegeneration biomarkers; Neurogranin; NFL}},
  language     = {{eng}},
  pages        = {{80--91}},
  publisher    = {{Elsevier}},
  series       = {{Neurobiology of Aging}},
  title        = {{Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults}},
  url          = {{http://dx.doi.org/10.1016/j.neurobiolaging.2022.04.010}},
  doi          = {{10.1016/j.neurobiolaging.2022.04.010}},
  volume       = {{116}},
  year         = {{2022}},
}