Premium
P1‐205: Prediction of Conversion of Mild Cognitive Impairment to Dementia with Neuronally Derived Blood Exosome Protein Profile
Author(s) -
Winston Charisse N.,
Goetzl Edward J.,
Akers Jonny,
Carter Bob S.,
Rockenstien Edward,
Galasko Douglas R.,
Masliah Eliezer,
Rissman Robert A.
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.953
Subject(s) - exosome , neuropathology , microvesicles , neurogranin , dementia , gene silencing , hippocampus , antibody , chemistry , cognitive impairment , medicine , pathology , immunology , microrna , biochemistry , disease , phosphorylation , gene , protein kinase c
Background: Levels of AD-related proteins in plasma neuronalderived exosomes (NDEs) were quantified to identify biomarkers for staging in AD. Additionally, plasma NDEs were injected in naive mice to determine the pathogenic potential of NDE cargo. Methods: Plasma exosomes were extracted, precipitated and enriched for neuronal source by anti-L1CAM antibody absorption. NDEs were characterized by size (Nanosight) and shape (TEM), and extracted NDE protein biomarkers were quantified by ELISAs. One month post injection, characterization of NDE cargo was conducted using IHC. Results: Plasma NDE levels of P-T181-tau, PS396-tau, and Ab1-42 were significantly higher, whereas those of neurogranin (NRGN) and the repressor element 1-silencing transcription factor (REST) were significantly lower in AD and MCI converting to AD (ADC) patients compared to cognitively-normal controls (CNC) and stable MCI (MCI) patients. Mice injected with NDEs from AD plasma displayed p-tau (PHF-1 antibody)-positive cells in the CA1 region of the hippocampus. Conclusions:Abnormal NDE levels of P-tau, Ab1-42, NRGN, and REST demonstrated high predictive accuracy for the conversion of MCI to AD dementia. NDE from demented patients seeded tau aggregation and induced neuropathology in normal mouse CNS.