Amyloidogenic Nanoplaques in Cerebrospinal Fluid: Relationship to Amyloid Brain Uptake and Clinical Alzheimer's Disease in a Memory Clinic Cohort.

ABSTRACT:

Background

Aggregation of amyloid-? (A?) is an early pathological event in Alzheimer's disease (AD). Consequently, measures of pathogenic aggregated A? are attractive biomarkers for AD. Here, we use a recently developed Thioflavin-T-Fluorescence Correlation Spectroscopy (ThT-FCS) assay to quantify structured ThT-responsive protein aggregates, so-called nanoplaques, in the cerebrospinal fluid (CSF).

Objective

The overall aim of this work was to assess whether ThT-FCS determined CSF nanoplaque levels could predict amyloid brain uptake as determined by 18F-Flutemetamol PET analysis. Further, we assess whether nanoplaque levels could predict clinical AD.

Methods

Nanoplaque levels in the CSF from 54 memory clinic patients were compared between sub-groups classified by 18F-Flutemetamol PET as amyloid-positive or amyloid-negative, and by clinical assessment as AD or non-AD.

Results

Nanoplaque levels did not differ between amyloid groups and could not predict brain amyloid uptake. However, nanoplaque levels were significantly increased in patients with clinical AD, and were significant predictors for AD when adjusting for age, sex, cognitive function, and apolipoprotein E (APOE) genotype.

Conclusion

The concentration of nanoplaques in the CSF differentiates patients with clinical AD from non-AD patients.

SUBMITTER: Aksnes M 

PROVIDER: S-EPMC7592690 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature