Publication

Protein fibril length in cerebrospinal fluid is increased in Alzheimer's disease.

Journal Paper/Review - Mar 8, 2023

Units
PubMed
Doi
Contact

Citation
Nirmalraj P, Schneider T, Lüder L, Felbecker A. Protein fibril length in cerebrospinal fluid is increased in Alzheimer's disease. Commun Biol 2023; 6:251.
Type
Journal Paper/Review (English)
Journal
Commun Biol 2023; 6
Publication Date
Mar 8, 2023
Issn Electronic
2399-3642
Pages
251
Brief description/objective

Alzheimer's disease (AD) associated proteins exist in cerebrospinal fluid (CSF). This paper evidences that protein aggregate morphology distinctly differs in CSF of patients with AD dementia (ADD), mild cognitive impairment due to AD (MCI AD), with subjective cognitive decline without amyloid pathology (SCD) and with non-AD MCI using liquid-based atomic force microscopy (AFM). Spherical-shaped particles and nodular-shaped protofibrils were present in the CSF of SCD patients, whereas CSF of ADD patients abundantly contained elongated mature fibrils. Quantitative analysis of AFM topographs confirms fibril length is higher in CSF of ADD than in MCI AD and lowest in SCD and non-AD dementia patients. CSF fibril length is inversely correlated with CSF amyloid beta (Aβ) 42/40 ratio and CSF p-tau protein levels (obtained from biochemical assays) to predict amyloid and tau pathology with an accuracy of 94% and 82%, respectively, thus identifying ultralong protein fibrils in CSF as a possible signature of AD pathology.