期刊
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
卷 6, 期 12, 页码 2518-2530出版社
WILEY
DOI: 10.1002/acn3.50948
关键词
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资金
- Health Department of the Government of Catalonia [PERIS SLT002/16/00408]
- Instituto de Salud Carlos III, Spain [PI11/02526, PI14/01126, PI17/01019, PI13/01532, PI16/01825, PI15/01618, PI18/00435, PI14/1561, PI17/01896, AC14/00013]
- CIBERNED program
- Fondo Europeo de Desarrollo Regional (FEDER)
- Marato TV3 grant [20141210, 044412, 20143710, 20143810]
- Generalitat de Catalunya [2014SGR-0235, SLT002/16/00408, SLT006/17/00119]
- Fundacion BBVA
- Fundacio Bancaria La Caixa
- European Social Fund
- Global Brain Health Institute
- Departament de Salut de la Generalitat de Catalunya [PERIS 20162020 SLT002/16/00329]
- Accion estrategica en Salud
- Union Europea, Una manera de hacer Europa
Objective: We aimed to investigate the relationship between cerebrospinal fluid levels (CSF) of amyloid precursor protein (APP)-derived peptides related to the amyloidogenic pathway, cortical thickness, neuropsychological performance, and cortical gene expression profiles in frontotemporal lobar degeneration (FTLD)-related syndromes, Alzheimer's disease (AD), and healthy controls. Methods: We included 214 participants with CSF available recruited at two centers: 93 with FTLD-related syndromes, 57 patients with AD, and 64 healthy controls. CSF levels of amyloid beta (A beta)1-42, A beta 1-40, A beta 1-38, and soluble beta fragment of APP (sAPPP) were centrally analyzed. We compared CSF levels of APP-derived peptides between groups and, we studied the correlation between CSF biomarkers, cortical thickness, and domain-specific cognitive composites in each group. Then, we explored the relationship between cortical thickness, CSF levels of APP-derived peptides, and regional gene expression profile using a brain-wide regional gene expression data in combination with gene set enrichment analysis. Results: The CSF levels of A beta 1-40, A beta 1-38, and sAPPP were lower in the FTLD-related syndromes group than in the AD and healthy controls group. CSF levels of all APP-derived peptides showed a positive correlation with cortical thickness and the executive cognitive composite in the FTLD-related syndromes group but not in the healthy control or AD groups. In the cortical regions where we observed a significant association between cortical thickness and CSF levels of APP-derived peptides, we found a reduced expression of genes related to synaptic function. Interpretation: APP-derived peptides in CSF may reflect FTLD-related neurodegeneration. This observation has important implications as A beta 1-42 levels are considered an indirect biomarker of cerebral amyloidosis.
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