Proteomic correlates of cortical thickness in cognitively normal individuals with normal and abnormal cerebrospinal fluid beta-amyloid1-42

• Published in: Neurobiology of aging Vol. 107; pp. 42 - 52
• Main Authors: Ekblad, Laura L., Visser, Pieter Jelle, Tijms, Betty M.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2021
• Subjects: Alzheimer´s disease; Biological pathway; Cerebrospinal fluid; Cognitively normal; cortical atrophy; Medicin och hälsovetenskap; Proteomics; Cognitively normal; CAA; AD; Cerebrospinal fluid; p-tau; Aβ; Alzheimer´s disease; WMH; Proteomics; CSF; t-tau; cortical atrophy; Biological pathway
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2021.07.003

•Associations between regional cortical thickness and cerebrospinal fluid (CSF) proteins were evaluated.•Cognitively normal individuals with normal and abnormal CSF Aβ42 were studied.•CSF Aβ42 modulated the associations between cortical thickness and CSF proteins.•Aβ42 specific associations were found in regions of early amyloid accumulation.•Aβ42 associations related to amyloid accumulation and inflammatory pathways. Cortical atrophy is an early feature of Alzheimer´s disease (AD). The biological processes associated with variability in cortical thickness remain largely unknown. We studied 220 cerebrospinal fluid (CSF) proteins to evaluate biological pathways associated with cortical thickness in 34 brain regions in 79 cognitively normal older individuals with normal (>192 ng/L, n = 47), and abnormal (≤192 ng/L, n = 32) CSF beta-amyloid1-42 (Aβ42). Interactions for Aβ42 status were tested. Panther GeneOntology and Cytoscape ClueGO analyses were used to evaluate biological processes associated with regional cortical thickness. 170 (77.3 %) proteins related with cortical thickness in at least 1 brain region across the total group, and 171 (77.7 %) proteins showed Aβ42 specific associations. Higher levels of proteins related to axonal and synaptic integrity, amyloid accumulation, and inflammation were associated with thinner cortex in lateral temporal regions, the rostral anterior cingulum, the lateral occipital cortex and the pars opercularis only in the abnormal Aβ42 group. Alterations in CSF proteomics are associated with a regional cortical atrophy in the earliest stages of AD. [Display omitted]