{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:08:04Z","timestamp":1791223684153,"version":"4.1.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T00:00:00Z","timestamp":1734048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CSF concentrations of \u03b2-amyloid 42 (A\u03b242) and phosphorylated tau (p-tau) are well-established biomarkers of Alzheimer\u2019s disease and have been studied in relation to several neuropathological features both in patients and in cognitively unimpaired individuals. The CSF p-tau\/A\u03b242 ratio, a biomarker combining information from both pathophysiological processes, has emerged as a promising tool for monitoring disease progression, even at pre-clinical stages. Here, we studied the association between the CSF p-tau\/A\u03b242 ratio with downstream markers of pre-clinical Alzheimer\u2019s disease progression including brain structure, glucose metabolism, fibrillary A\u03b2 deposition and cognitive performance in 234 cognitively unimpaired individuals, who underwent cognitive testing, a lumbar puncture, MRI, 18F-fluorodeoxyglucose and 18F-flutemetamol PET scanning. We evaluated both main effects and interactions with Alzheimer\u2019s disease risk factors, such as older age, female sex and the apoliporoptein E (APOE)-\u025b4 allele, in a priori defined regions of interest and further examined the associations on the whole-brain using voxel-wise regressions. In addition, as the association between CSF Alzheimer\u2019s disease biomarkers and brain structure and function may be non-linear, we tested the interaction between the CSF p-tau\/A\u03b242 ratio and stages of pre-clinical Alzheimer\u2019s disease defined using the amyloid (A) and tau (T) classification. We found significantly positive associations between CSF p-tau\/A\u03b242 and both cortical A\u03b2 deposition and regional grey matter volume while no effect was observed for brain metabolism. A significant interaction with age indicated that, for the same level of CSF p-tau\/A\u03b242, older individuals displayed both increased A\u03b2 deposition and lower grey matter volume, in widespread cortical areas. In addition, we found that women compared with men had a greater A\u03b2 fibrillary accumulation in midline cortical areas and inferior temporal regions, for the same level of the CSF biomarker. The impact of CSF p-tau\/A\u03b242 on grey matter volume was modulated by AT stages, with A+T+ individuals displaying significantly less positive associations in areas of early atrophy in the Alzheimer\u2019s continuum. Finally, we found that sex and APOE-\u025b4 modulated the association between the CSF biomarker and episodic memory as well as abstract reasoning, respectively. Our data indicate that the CSF p-tau\/A\u03b242 ratio is strongly associated with multiple downstream neuropathological events in cognitively unimpaired individuals and may thus serve as a potent biomarker to investigate the earliest changes in pre-clinical Alzheimer\u2019s disease. Given that its impact on both A\u03b2 deposition and grey matter volume is modulated by specific risk factors, our results highlight the need to take into account such predisposing variables in both clinical practice and prevention trials.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae451","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T14:02:22Z","timestamp":1734098542000},"source":"Crossref","is-referenced-by-count":10,"title":["The CSF p-tau\/\u03b2-amyloid 42 ratio correlates with brain structure and fibrillary \u03b2-amyloid deposition in cognitively unimpaired individuals at the earliest stages of pre-clinical Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9216-949X","authenticated-orcid":false,"given":"Raffaele","family":"Cacciaglia","sequence":"first","affiliation":[{"name":"Barcelona\u03b2eta Brain Research Center (BBRC), Pasqual Maragall Foundation , Barcelona 08005 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