Year: 2019
Type: article
Abstract: CSF tau and tau PET may have different dynamics in AD. 58 cognitively unimpaired (CDR 0, 21 Aβ- and 37 Aβ+), 38 CDR 0.5 (all Aβ+), 33 AD CDR 1–3 (all Aβ+), and 71 non-AD neurodegenerative patients from the BioFINDER study were examined with CSF T-tau and P-tau and 18F-Flortaucipir tau PET. 55 subjects had an additional early CSF sample (mean 3.7 years before PET), and 52 subjects had a second 18F-Flortaucipir scan (mean 1.9 years after the first scan). We also measured CSF T-tau in WT and 5xFAD mice, at 2–12 months. T-tau and P-tau were increased in CDR 0 Aβ+, and further increased in CDR 0.5 and CDR 1-3, while 18F-Flortaucipir was not increased in CDR 0 Aβ+, but increased step-wise from CDR 0.5 to 1–3 (Fig 1). At a priori cut-points, P-tau had the highest sensitivity for CDR 0 Aβ+ (43%) and CDR 0.5 (92%), while 18F-Flortaucipir (in inferior temporal cortex) had the highest sensitivity for CDR 1–3 (100%). A relatively large proportion of subjects were isolated CSF P-tau+, especially in Aβ+ CDR 0.0−0.5 cases (Fig 2). Longitudinal rates of CSF tau were increased in CDR 0 Aβ+, even in cases that were 18F-Flortaucipir negative 2–4 years later. High CSF tau, but not baseline 18F-Flortaucipir, independently predicted increased rates of 18F-Flortaucipir uptake in CDR 0.5-3 cases (Fig 3). In mediation analyzes, the effects of Aβ-pathology on 18F-Flortaucipir was mediated via CSF P-tau. In 5xFAD mice CSF tau increased from 4 months which was associated with widespread Aβ-containing plaques even though this model does not develop tau aggregates (Fig 4). 18F-Flortaucipir was more strongly associated with MMSE and atrophy than CSF tau (Fig 5), and was also associated with longitudinal decline in MMSE.
Source: Alzheimer s & Dementia
Institutions: Lund University, Sahlgrenska University Hospital
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2980440668