Development of CSF/plasma biomarker which can predict onset of Alzheimer's disease

Not Applicable

Recruiting

• Conditions: Alzheimer' s disease

• Registration Number: JPRN-UMIN000025008
• Lead Sponsor: Osaka University

Brief Summary

Surrogate markers for the Alzheimer disease (AD)-associated 42-amino acid form of amyloid-beta (Abeta42) have been sought because they may aid in the diagnosis of AD and for clarification of disease pathogenesis. Here, we demonstrate that human cerebrospinal fluid (CSF) contains three APLP1-derived Abeta-like peptides (APL1beta) that are generated by beta- and gamma-cleavages at a concentration of approximately 4.5 nM. These novel peptides, APL1beta25, APL1beta27 and APL1beta28, were not deposited in AD brains. Interestingly, most gamma-secretase modulators (GSMs) and familial AD-associated presenilin1 mutants that up-regulate the relative production of Abeta42 cause a parallel increase in the production of APL1beta28 in cultured cells. Moreover, in CSF from patients with pathological mutations in presenilin1 gene, the relative APL1beta28 levels are higher than in non-AD controls, while the relative Abeta42 levels are unchanged or lower. Most strikingly, the relative APL1beta28 levels are higher in CSF from sporadic AD patients (regardless of whether they are at mild cognitive impairment or AD stage), than those of non-AD controls. Based on these results, we propose the relative level of APL1beta28 in the CSF as a candidate surrogate marker for the relative level of Abeta42 production in the brain.

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-12-12
• Last Update Posted: 17 October 2023

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

Not provided

Exclusion Criteria

not particular

Study & Design

• Study Type: Interventional
• Study Design: Not specified