Clinical utility of CSF Aβ38 in Japanese research and clinical cohorts

Abstract

Abstract INTRODUCTION Previous studies have reported that cerebrospinal fluid (CSF) amyloid beta (Aβ42/Aβ38) performs comparably to Aβ42/Aβ40 in predicting amyloid positron emission tomography (PET) positivity in White cohorts. However, this finding has not been validated in diverse populations. Moreover, the utility of CSF Aβ38 in diagnosing various neurological diseases has not been fully understood. METHODS We analyzed CSF Aβ38, Aβ40, Aβ42, phosphorylated tau181, and neurofilament light chain in Japanese research and clinical cohorts with Alzheimer's clinical syndrome (ACS) or non‐ACS. RESULTS CSF Aβ42/Aβ38 predicted amyloid PET positivity comparably to Aβ42/Aβ40. The levels of CSF Aβ38 were significantly lower in patients with progressive supranuclear palsy (PSP) and idiopathic normal pressure hydrocephalus (iNPH) than in those with other diseases. DISCUSSION We validated the high diagnostic performance of CSF Aβ42/Aβ38 in Japanese patients with AD. CSF Aβ38 reduction may be a characteristic feature of PSP and iNPH. Highlights The diagnostic value of cerebrospinal fluid (CSF) amyloid beta (Aβ)38 was examined in Japanese research and clinical cohorts. CSF Aβ42/Aβ38 and Aβ42/Aβ40 showed comparable performance to detect brain Aβ deposition. CSF Aβ42/Aβ38 and Aβ42/Aβ40 discordant group showed a characteristic profile. CSF Aβ38 and Aβ40 were prominently decreased in progressive supranuclear palsy and idiopathic normal pressure hydrocephalus.

Keywords

• Alzheimer's disease continuum
• amyloid beta 38
• cerebrospinal fluid
• idiopathic normal pressure hydrocephalus
• progressive supranuclear palsy