Clinical and neuropathological associations of plasma Aβ/Aβ, p-tau217 and neurofilament light in sporadic frontotemporal dementia spectrum disorders.

INTRODUCTION

Plasma amyloid beta/amyloid beta (Aβ/Aβ) and phosphorylated tau217 (p-tau217) identify individuals with primary Alzheimer's disease (AD). They may detect AD co-pathology in the setting of other primary neurodegenerative diseases, but this has not been systematically studied.

METHODS

We compared the clinical, neuroimaging, and neuropathological associations of plasma Aβ/Aβ (mass spectrometry), p-tau217 (electrochemiluminescence), and neurofilament light ([NfL], single molecule array [Simoa]), as markers of AD co-pathology, in a sporadic frontotemporal dementia (FTD) cohort ( = 620).

RESULTS

Aβ/Aβ showed no clinicopathological associations. High p-tau217 was present in amnestic dementia (AmD) presumed to be due to FTD, logopenic primary progressive aphasia (lvPPA), and carriers, and correlated with worse baseline and longitudinal clinical scores, lower hippocampal volumes, and more severe AD co-pathology (Braak Stage). NfL was elevated in all FTD phenotypes, and correlated with clinical scores and frontotemporal brain volumes.

DISCUSSION

Plasma p-tau217 has clinical, neuroimaging, and neuropathological correlates in sporadic FTD and may identify FTD cases with AD co-pathology.

HIGHLIGHTS

Alzheimer's disease (AD) features could be identified with plasma phosphorylated tau217 (p-tau217) in frontotemporal lobar degeneration (FTLD).Plasma p-tau217 is a better discriminator of AD co-pathology and AD-associated features in FTLD than plasma amyloid beta/amyloid beta (Aβ/Aβ) and neurofilament light (NfL).In FTLD, plasma p-tau217, but not Aβ/Aβ or neurofilament light, has phenotypical, neurocognitive, and neuroimaging correlates suggestive of AD co-pathology.