TY - JOUR
T1 - Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults
AU - Vidal-Piñeiro, Didac
AU - Sørensen, Øystein
AU - Blennow, Kaj
AU - Capogna, Elettra
AU - Halaas, Nathalie Bodd
AU - Idland, Ane Victoria
AU - Mowinckel, Athanasia Monica
AU - Pereira, Joana Braga
AU - Watne, Leiv Otto
AU - Zetterberg, Henrik
AU - Walhovd, Kristine Beate
AU - Fjell, Anders Martin
AU - Alzheimer's Disease Neuroimaging Initiative
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Cognitively healthy older adults
KW - CSF
KW - FABP3
KW - Neurodegeneration biomarkers
KW - Neurogranin
KW - NFL
U2 - 10.1016/j.neurobiolaging.2022.04.010
DO - 10.1016/j.neurobiolaging.2022.04.010
M3 - Article
C2 - 35584575
AN - SCOPUS:85130362638
SN - 0197-4580
VL - 116
SP - 80
EP - 91
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -