Cargo proteins of plasma astrocyte‐derived exosomes in Alzheimer's disease

  title={Cargo proteins of plasma astrocyte‐derived exosomes in Alzheimer's disease},
  author={Edward J. Goetzl and Maja Mustapic and Dimitrios Kapogiannis and Erez Eitan and Irina V. Lobach and Laura Goetzl and Janice B Schwartz and Bruce L Miller},
  journal={The FASEB Journal},
  pages={3853 - 3859}
Efficient intercellular transfer of RNAs, proteins, and lipids as protected exosomal cargo has been demonstrated in the CNS, but distinct physiologic and pathologic roles have not been well defined for this pathway. The capacity to isolate immunochemically human plasma neuron‐derived exosomes (NDEs), containing neuronspecific cargo, has permitted characterization of CNS‐derived exosomes in living humans. Constituents of the amyloid β‐peptide (Aβ)42‐generating system now are examined in 2… 

Advancing medicine for Alzheimer’s disease: A plasma neural exosome platform

  • E. Goetzl
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2020
Neurally derived extracellular vesicle protein abnormalities also reveal a range of later amplification processes that encompasses insulin resistance, lysosomal defects, decreased survival factors, increased reactive oxygen species, and excessive neuroinflammation.

Implications of exosomes derived from cholesterol-accumulated astrocytes in Alzheimer's disease pathology

It is suggested that exosomes derived from cholesterol-accumulated astrocytes can play an important role in trafficking APP/Aβ peptides and influencing neuronal viability in the affected regions of the AD brain.

Synaptic Activity and (Neuro)Inflammation in Alzheimer's Disease: Could Exosomes be an Additional Link?

It is hypothesize that exosomes may participate in the control of neuronal excitability via inflammatory-like mechanisms both at the central level and from the periphery.

Altered cargo proteins of human plasma endothelial cell–derived exosomes in atherosclerotic cerebrovascular disease

  • E. GoetzlJ. Schwartz G. Jicha
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2017
Elevated EDE and PDE levels of atherosclerosis‐promoting proteins in CeVD justify clinical studies of their potential value as biomarkers.

Potential Effects of MSC-Derived Exosomes in Neuroplasticity in Alzheimer’s Disease

How exosomes are involved in AD pathology and the therapeutic potential of MSC-derived exosome mediated by miRNA and protein cargo are described and discussed.

Mitochondrial RNA in Alzheimer’s Disease Circulating Extracellular Vesicles

It is proposed that in the AD brain, toxicity-causing mitochondrial damage results in the packaging of mitochondrial components for export in EVs and further proposed that mt-RNAs in plasma EVs can be diagnostic and prognostic biomarkers for MCI and AD.

Deficient neurotrophic factors of CSPG4‐type neural cell exosomes in Alzheimer disease

It is suggested that CSPG4 cells export in exosomes higher levels of neurotrophic factors than neurons or astrocytes and that C SPG4E neurotrophic Factors are diminished early in AD, with no significant progression of decreases later in the course.

Neural cell‐derived plasma exosome protein abnormalities implicate mitochondrial impairment in first episodes of psychosis

Drugs that increase depressed levels of proteins and mimetics of deficient short open‐reading frame peptides may be of therapeutic value in early phases of schizophrenia.

Extracellular vesicles: where the amyloid precursor protein carboxyl‐terminal fragments accumulate and amyloid‐β oligomerizes

It is found that full‐length APP is cleaved in EVs incubated in the absence of cells, and this may contribute to efficient removal of neurotoxic peptides from the brain.



Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease

Levels of autolysosomal proteins in neurally derived blood exosomes distinguish patients with AD from case controls and appear to reflect the pathology of AD up to 10 years before clinical onset.

Astrocytic expression of the Alzheimer's disease β‐secretase (BACE1) is stimulus‐dependent

To address the question whether astrocytic BACE1 expression is an event specifically triggered by β‐amyloid plaques or whether glial cell activation by other mechanisms also induces Bace1 expression, six different experimental strategies to activate brain glial cells acutely or chronically are used.

Dysfunctionally phosphorylated type 1 insulin receptor substrate in neural‐derived blood exosomes of preclinical Alzheimer's disease

  • D. KapogiannisA. Boxer E. Goetzl
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2015
Insulin resistance reflected in R values from this blood test is higher for patients with AD, DM2, and FTD than case control subjects; higher for Patients with AD than patients with DM2 or FTD; and accurately predicts development of AD up to 10 yr prior to clinical onset.

Single-Cell Detection of Secreted Aβ and sAPPα from Human IPSC-Derived Neurons and Astrocytes

A method for detecting analytes secreted from single human induced pluripotent stem cell (iPSC)-derived neural cells is presented and it is shown that astrocytes are competent to secrete high levels of Aβ and therefore may be a significant contributor to Aβ accumulation in the brain.

The contribution of activated astrocytes to Aβ production: Implications for Alzheimer's disease pathogenesis

Cytokines including TNF-α+IFN-γ increase levels of endogenous BACE1, APP, and Aβ and stimulate amyloidogenic APP processing in astrocytes as well as oligomeric and fibrillar Aβ42, suggesting a cytokine- and A β42-driven feed-forward mechanism that promotes astroCytic Aβ production.

Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides

Phase-contrast and confocal microscopy show that Apoe−/− astrocytes do not respond to or internalize Aβ deposits to the same extent as do wild-type astroicytes, and Apoe seems to be important in the degradation and clearance of deposited Aβ species by astroCytes, a process that may be impaired in Alzheimer disease.

Relationship between ubiquilin-1 and BACE1 in human Alzheimer's disease and APdE9 transgenic mouse brain and cell-based models

SEPT8 modulates β-amyloidogenic processing of APP by affecting the sorting and accumulation of BACE1

Whether downregulation of septin (SEPT) protein family members, which are implicated in synaptic plasticity and vesicular trafficking, affects APP processing and Aβ generation is elucidated and SEPT8 modulates β-amyloidogenic processing of APP by affecting BACE1.

Transcriptional Regulation of BACE1 by NFAT3 Leads to Enhanced Amyloidogenic Processing

This report found that both BACE1 and NFAT3 levels were significantly increased in the brains of APP/PS1 transgenic mice and indicated that NFAT is a Bace1 transcription factor, suggesting that inhibition of NFAT-mediated BACE 1 expression may be a valuable drug target for AD therapy.