TY - JOUR
T1 - Neuronal-Derived EV Biomarkers Track Cognitive Decline in Alzheimer’s Disease
AU - Eren, Erden
AU - Leoutsakos, Jeannie Marie
AU - Troncoso, Juan
AU - Lyketsos, Constantine G.
AU - Oh, Esther S.
AU - Kapogiannis, Dimitrios
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - The hallmarks of Alzheimer’s disease (AD) pathology are senile plaques containing amyloid-beta (Aβ) and neurofibrillary tangles containing hyperphosphorylated tau. Additional pathologies often co-exist, whereas multiple pathogenic mechanisms are involved in AD, especially synaptic degeneration, which necessitate the need for synaptic integrity-related biomarkers along-side Aβ-and tau-related biomarkers. Plasma neuron-derived Extracellular Vesicles EVs (NDEVs) provide biomarkers related to Aβ and tau and synaptic degeneration. Here, to further establish the latter as a “liquid biopsy” for AD, we examined their relationship with ante-mortem cognition in pathologically-confirmed AD cases. We immunoprecipitated NDEVs by targeting neuronal marker L1CAM from ante-mortem plasma samples from 61 autopsy-confirmed cases of pure AD or AD with additional pathologies and measured Aβ42, p181-Tau, total Tau, synaptophysin, synaptopodin and three canonical EV markers, CD63, CD81 and CD9. Higher NDEV Aβ42 levels were consistently associated with better cognitive status, memory, fluency, working memory and executive function. Higher levels of NDEV synaptic integrity-related biomarkers were associated with better performance on executive function tasks. Our findings motivate the hypothesis that releasing Aβ42-laden NDEVs may be an adaptive mechanism in AD.
AB - The hallmarks of Alzheimer’s disease (AD) pathology are senile plaques containing amyloid-beta (Aβ) and neurofibrillary tangles containing hyperphosphorylated tau. Additional pathologies often co-exist, whereas multiple pathogenic mechanisms are involved in AD, especially synaptic degeneration, which necessitate the need for synaptic integrity-related biomarkers along-side Aβ-and tau-related biomarkers. Plasma neuron-derived Extracellular Vesicles EVs (NDEVs) provide biomarkers related to Aβ and tau and synaptic degeneration. Here, to further establish the latter as a “liquid biopsy” for AD, we examined their relationship with ante-mortem cognition in pathologically-confirmed AD cases. We immunoprecipitated NDEVs by targeting neuronal marker L1CAM from ante-mortem plasma samples from 61 autopsy-confirmed cases of pure AD or AD with additional pathologies and measured Aβ42, p181-Tau, total Tau, synaptophysin, synaptopodin and three canonical EV markers, CD63, CD81 and CD9. Higher NDEV Aβ42 levels were consistently associated with better cognitive status, memory, fluency, working memory and executive function. Higher levels of NDEV synaptic integrity-related biomarkers were associated with better performance on executive function tasks. Our findings motivate the hypothesis that releasing Aβ42-laden NDEVs may be an adaptive mechanism in AD.
KW - Alzheimer’s disease
KW - Autopsy
KW - Exosomes
KW - Extracellular vesicles
KW - Mixed pathology
KW - Neuron-derived extracellular vesicles
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U2 - 10.3390/cells11030436
DO - 10.3390/cells11030436
M3 - Article
C2 - 35159246
AN - SCOPUS:85123353022
SN - 2073-4409
VL - 11
JO - Cells
JF - Cells
IS - 3
M1 - 436
ER -