[P3–218]: Tau Plasma Levels in Subjective Cognitive Decline: Results From the Delcode Study

Abstract

Previous studies have demonstrated increased tau plasma levels in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) due to AD. Much less is known whether increased tau plasma levels can already be detected in the pre-MCI stage of subjective cognitive decline (SCD). In the present study we measured tau plasma levels in 111 SCD patients and 134 age-and gendermatched cognitively healthy controls participating in the DZNE (German Center for Neurodegenerative Diseases) longitudinal study on cognition and dementia (DELCODE). Tau plasma levels were measured using ultra-sensitive, single-molecule array (Simoa) technology. We found no significant different tau plasma levels in SCD (3.4 pg/ml) compared with healthy controls (3.6 pg/ml) after controlling for age, gender, and education (p = 0.137). In addition, tau plasma levels did not correlate with Aβ42 (r = 0.073; p = 0.634), tau (r = −0.179; p = 0.240), and p-tau181 (r = −0.208; p = 0.171) cerebrospinal fluid (CSF) levels in a subgroup of 45 SCD patients with available CSF. In conclusion, plasma tau is not increased in SCD patients. In addition, the lack of correlation between tau in plasma and CSF in the examined cohort suggests that tau levels are affected by different factors in both biofluids.Brain deposition of neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau is a hallmark of Alzheimer's disease (AD) pathology 1 . Several tau tracers for positron emission tomography (PET) imaging including 18F-TH523 have been developed over the past few years 2 . As in the brain itself, tau levels in the cerebrospinal fluid (CSF) were found to be increased in AD patients 3 . Therefore, CSF tau provides a useful marker of tau pathology. Several tau-based therapeutic approaches are currently investigated. Thus, detection of tau levels holds enormous potential for both early diagnosis of AD and monitoring of disease-modifying therapeutics.

Biomarkers associated with the pathogenesis of Alzheimer’s disease

“…Overexpression of sTREM2 attenuated tau pathology and cognitive impairment in tau P301S transgenic mice. In addition, sTREM2 ( Laske et al, 2017 ; Hampel et al, 2018 ; Hansson et al, 2018 ; Lleo et al, 2019 ; Doecke et al, 2020 ; Aamodt et al, 2021 ; Clark et al, 2021 ; Simrén et al, 2021 ; Park et al, 2022 ; Zhang et al, 2022 ; Delaby et al, 2023 ; Dinoto et al, 2023 ; Pena-Bautista et al, 2023 ) is the smallest sTREM2 sequence that activates TG2 ( Zhang et al, 2023 ). This active peptide mimics the protective effects of sTREM2 both in vitro and in vivo .…”

“…P-tau and t-tau in the CSF are connected to AD disease, with t-tau reflecting neurological damage and p-tau reflecting the extent of phosphorylated tau protein deposition in the brain. Increased concentrations of phosphorylated tau in the brain have been connected to a progressive reduction in cognitive function, and research has shown that p-tau concentrations in the CSF are 3.4 times larger in AD patients than in healthy controls, while elevated t-tau is not connected to the course of the disease ( Toledo et al, 2011 ; Laske et al, 2017 ; Müller et al, 2017 ; Clark et al, 2021 ; Frank et al, 2022 ). The assay for p-tau protein in the CSF focused on phosphorylation sites such as Thr181, which showed that the CSF in AD patients had significantly increased ( Delaby et al, 2023 ).…”

“…After nerve damage, NFL is released from neurons into the blood and CSF, so NFL reflects neurodegeneration ( Laske et al, 2017 ; Hampel et al, 2018 ; McGrowder et al, 2021 ). The development of highly sensitive techniques to detect even low levels of NFL in the blood has made NFL an accessible and reliable biomarker of neurodegenerative disease ( Dinoto et al, 2023 ).…”