Synergistic role of white matter changes and CSF biomarkers in amnestic and non‐amnestic AD phenotypes

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is pathologically diagnosed based on abnormal amyloid and tau pathology but is also related to additional pathologic processes. (1) The cognitive symptoms are not directly associated with AD pathology but are the consequence of a complex mechanism, showing discordance between clinical symptoms and CSF biomarkers. (2) Previous evidence suggests a range from the synergistic role of white matter signal abnormality (WMSA) and CSF biomarkers on AD to no relationship between the two. (1) We aimed to analyze the CSF biomarker profiles, and brain MRI changes in AD patients with different phenotypes.MethodCSF was collected by lumbar puncture from 40 individuals with AD. We analyzed CSF levels (Aβ‐42, Aβ‐40, t‐tau, p‐tau, tau / Aβ‐42, and Aβ‐42/40) in two different samples. The clinical characteristics included: AD phenotype (amnestic or non‐amnestic), age, gender, education, and age‐onset. We used the brain MRI scales: MTA (mesial temporal lobe atrophy), and Fazekas, for white matter signal abnormality (WMSA), considering pathological changes (≥ 2).ResultPreliminary results in 16 patients showed that most of the patients with CSF typical AD pattern presented an amnestic phenotype, revealing WMSA changes. The patients with no CSF changes showed little or no WMSA changes in both clinical presentations. The amnestic phenotype showed more MTA changes in patients with typical AD CSF pattern, and no difference was found between the phenotypes in patients with no CSF changes.ConclusionIt can be a positive relation between cerebrovascular diseases, WMSA changes, and CSF pathological changes in AD, regardless of the phenotype, supporting that Aβ pathology may lead to secondary vascular damage including white matter lesions.