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Similar alterations can, however, also be observed in cognitively intact older subjects and may prelude the clinical manifestation of AD<\/jats:styled-content>. The objectives of this prospective cross\u2010sectional study in a cohort of 38 cognitively intact older adults were twofold: (i) to investigate the latent relationship among cerebrospinal fluid (CSF<\/jats:styled-content>) biomarkers reflecting the main pathophysiological processes of AD<\/jats:styled-content>, and (ii) to assess the correlation between these biomarkers and gray matter volume as well as amyloid load. All subjects underwent extensive neuropsychological examinations, CSF<\/jats:styled-content> sampling, [18<\/jats:sup>F]\u2010flutemetamol amyloid positron emission tomography, and T1<\/jats:sub>\u2010weighted magnetic resonance imaging. A factor analysis revealed one factor that explained most of the variance in the CSF<\/jats:styled-content> biomarker dataset clustering t\u2010tau, \u03b1\u2010synuclein, p\u2010tau181<\/jats:sub>, neurogranin, BACE<\/jats:styled-content>1, visinin\u2010like protein 1, chitinase\u20103\u2010like protein 1 (YKL<\/jats:styled-content>\u201040), A\u03b21\u201340<\/jats:sub> and A\u03b21\u201338<\/jats:sub>. Higher scores on this factor correlated with lower gray matter volume and with higher amyloid load in the precuneus. At the level of individual CSF<\/jats:styled-content> biomarkers, levels of visinin\u2010like protein 1, neurogranin, BACE<\/jats:styled-content>1, A\u03b21\u201340<\/jats:sub>, A\u03b21\u201338,<\/jats:sub> and YKL<\/jats:styled-content>\u201040 all correlated inversely with gray matter volume of the precuneus. These findings demonstrate that in cognitively intact older subjects, CSF<\/jats:styled-content> levels of synaptic and neuronal integrity biomarkers, amyloidogenic processing and measures of innate immunity (YKL<\/jats:styled-content>\u201040) display a latent structure of common variance, which is associated with loss of structural integrity of brain regions implicated in the earliest stages of AD<\/jats:styled-content>.<\/jats:p><\/jats:sec>Open Science Badges<\/jats:title><\/jats:p>This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript, and for *Preregistration* because the study was pre\u2010registered at https:\/\/osf.io\/7qm9t\/<\/jats:ext-link>. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https:\/\/cos.io\/our-services\/open-science-badges\/<\/jats:ext-link>.<\/jats:p><\/jats:sec>\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14680","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T16:21:16Z","timestamp":1549383676000},"page":"139-157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Cerebrospinal fluid levels of synaptic and neuronal integrity correlate with gray matter volume and amyloid load in the precuneus of cognitively intact older adults"],"prefix":"10.1111","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2257-0568","authenticated-orcid":false,"given":"Jolien","family":"Schaeverbeke","sequence":"first","affiliation":[{"name":"Laboratory for Cognitive Neurology Department of Neurosciences KU Leuven Leuven 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