Aß42 |
- reduced levels in cerebrospinal fluid(CSF) of AD patients.3939 Jack CR Jr, Bennett DA, Blennow K, et al. A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology 2016;87(05):539–547. Doi: 10.1212/WNL.0000000000002923 https://doi.org/10.1212/WNL.000000000000...
- elevated levels in plasma isolated NDEVs from AD an MCI in comparison to controls.4444 Jia L, Qiu Q, Zhang H, et al. Concordance between the assessment of Aβ42, T-tau, and P-T181-tau in peripheral blood neuronalderived exosomes and cerebrospinal fluid. Alzheimers Dement 2019;15(08):1071–1080. Doi: 10.1016/j.jalz.2019.05.002 https://doi.org/10.1016/j.jalz.2019.05.0...
,4646 Winston CN, Goetzl EJ, Akers JC, et al. Prediction of conversion from mild cognitive impairment to dementia with neuronally derived blood exosome protein profile. Alzheimers Dement (Amst) 2016;3:63–72. Doi: 10.1016/j.dadm.2016.04.001 https://doi.org/10.1016/j.dadm.2016.04.0...
,4747 Fiandaca MS, Kapogiannis D, Mapstone M, et al. Identification of preclinical Alzheimer’s disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study. Alzheimers Dement 2015;11(06):600–7.e1. Doi: 10.1016/j.jalz.2014.06.008 https://doi.org/10.1016/j.jalz.2014.06.0...
,5151 Goetzl EJ, Kapogiannis D, Schwartz JB, et al. Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer’s disease. FASEB J 2016;30(12):4141–4148. Doi: 10.1096/fj.201600816R https://doi.org/10.1096/fj.201600816R...
- elevated levels in plasma isolated NDEVs from AD in comparison to controls up to 10 years prior to clinical diagnosis, with progressive increase of such levels along with disease progression.4747 Fiandaca MS, Kapogiannis D, Mapstone M, et al. Identification of preclinical Alzheimer’s disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study. Alzheimers Dement 2015;11(06):600–7.e1. Doi: 10.1016/j.jalz.2014.06.008 https://doi.org/10.1016/j.jalz.2014.06.0...
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Tau |
- inconclusive. |
Synaptic proteins |
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Neurogranin, Synaptotagmin, Synaptopodin and Synaptophysin |
- decreased levels in plasma isolated EVs from AD patients in comparison to controls(same in MCI and Parkinsons Disease).5151 Goetzl EJ, Kapogiannis D, Schwartz JB, et al. Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer’s disease. FASEB J 2016;30(12):4141–4148. Doi: 10.1096/fj.201600816R https://doi.org/10.1096/fj.201600816R...
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SNAP-25 and Synapsin-1 |
- decreased levels in plasma isolated EVs from AD patients in comparison to controls.5151 Goetzl EJ, Kapogiannis D, Schwartz JB, et al. Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer’s disease. FASEB J 2016;30(12):4141–4148. Doi: 10.1096/fj.201600816R https://doi.org/10.1096/fj.201600816R...
,5252 Agliardi C, Guerini FR, Zanzottera M, Bianchi A, Nemni R, ClericiM. SNAP-25 in SerumIs Carried by Exosomes of Neuronal Origin and Is a Potential Biomarker of Alzheimer’s Disease. Mol Neurobiol 2019;56(08):5792–5798. Doi: 10.1007/s12035-019-1501-x https://doi.org/10.1007/s12035-019-1501-...
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Neuronal pentraxin-2, Neurexin-2-α, GluA4-containing Glutamate receptor and Neuroligin-1 |
- reduced levels in plasma isolated NDEVs from AD patients in comparison to controls; the reduced levels correlated with cognitive loss; - the decreased levels of Neurexin-2-α, GluA4-containing Glutamate receptor and Neuroligin-1 were present up to 6-11 years before clinical diagnosis, and reduction was directly proportional to disease progression.5353 Goetzl EJ, Abner EL, Jicha GA, Kapogiannis D, Schwartz JB. Declining levels of functionally specialized synaptic proteins in plasma neuronal exosomes with progression of Alzheimer’s disease. FASEB J 2018;32(02):888–893. Doi: 10.1096/fj.201700731R https://doi.org/10.1096/fj.201700731R...
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Insulin metabolism proteins |
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Phospho-Ser312-IRS1 |
- elevated levels in NDEVs isolated from AD patients plasma.5454 Mullins RJ, Mustapic M, Goetzl EJ, Kapogiannis D. Exosomal biomarkers of brain insulin resistance associated with regional atrophy in Alzheimer’s disease. Hum Brain Mapp 2017;38(04): 1933–1940. Doi: 10.1002/hbm.23494 https://doi.org/10.1002/hbm.23494...
,5555 Kapogiannis D, Boxer A, Schwartz JB, et al. Dysfunctionally phosphorylated type 1 insulin receptor substrate in neural-derived blood exosomes of preclinical Alzheimer’s disease. FASEB J 2015;29(02):589–596. Doi: 10.1096/fj.14-262048 https://doi.org/10.1096/fj.14-262048...
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Phospho-panTyr-IRS1 |
- decreases levels in NDEVs isolated from AD patients plasma.5454 Mullins RJ, Mustapic M, Goetzl EJ, Kapogiannis D. Exosomal biomarkers of brain insulin resistance associated with regional atrophy in Alzheimer’s disease. Hum Brain Mapp 2017;38(04): 1933–1940. Doi: 10.1002/hbm.23494 https://doi.org/10.1002/hbm.23494...
,5555 Kapogiannis D, Boxer A, Schwartz JB, et al. Dysfunctionally phosphorylated type 1 insulin receptor substrate in neural-derived blood exosomes of preclinical Alzheimer’s disease. FASEB J 2015;29(02):589–596. Doi: 10.1096/fj.14-262048 https://doi.org/10.1096/fj.14-262048...
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Lysossomal proteins |
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Cathepsin D |
- increased levels in NDEVs isolated from AD and pre-clinical AD patients in comparison to controls.5656 Goetzl EJ, Boxer A, Schwartz JB, et al. Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease. Neurology 2015;85(01):40–47
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Heat shock protein-70 |
- reduced levels in NDEVs isolated from AD and pre-clinical AD patients in comparison to controls.5656 Goetzl EJ, Boxer A, Schwartz JB, et al. Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease. Neurology 2015;85(01):40–47
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Neurotrophic factors |
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Hepatocyte growth factor, Fibroblast growth factor type 2, Fibroblast growth factor type 13 and Insulin-like growth factor type 1 |
- reduced levels in neuron precursor cells(CSPG4) derived EVs isolated from the plasma of pre-clinical AD patients in comparison to controls.5757 Goetzl EJ, Nogueras-Ortiz C, Mustapic M, et al. Deficient neurotrophic factors of CSPG4-type neural cell exosomes in Alzheimer disease. FASEB J 2019;33(01):231–238
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Astrocytes |
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BACE-1 and sAPPß |
- elevated levels in astrocyte-derived EVs isolated from AD patientes in comparison to controls.5858 Goetzl EJ, Schwartz JB, Abner EL, Jicha GA, Kapogiannis D. High complement levels in astrocyte-derived exosomes of Alzheimer disease. Ann Neurol 2018;83(03):544–552
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Glia-derived neurotrophic factor(GNDF) |
- reduced levels in astrocyte-derived EVs isolated from AD patients in comparison to controles.5959 Goetzl EJ, Mustapic M, Kapogiannis D, et al. Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer’s disease. FASEB J 2016;30(11):3853–3859. Doi: 10.1096/fj.201600756R https://doi.org/10.1096/fj.201600756R...
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Micro-RNAs |
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miR-342-3p, miR-125a-5p, miR-125b-5p and miR-451a |
- reduced expression levels in exossomes isolated from AD patients in comparison to controls; expression levels directly correlates to cognitive defect.2929 Lugli G, Cohen AM, Bennett DA, et al. Plasma Exosomal miRNAs in Persons with and without Alzheimer Disease: Altered Expression and Prospects for Biomarkers. PLoS One 2015;10(10):e0139233. Doi: 10.1371/journal.pone.0139233 https://doi.org/10.1371/journal.pone.013...
6565 Rani A, O’Shea A, Ianov L, Cohen RA, Woods AJ, Foster TC. miRNA in circulating microvesicles as biomarkers for age-related cognitive decline. Front Aging Neurosci 2017;9:323
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miR-135a, miR-193b, miR-384 |
- combined analyses of expression in exossomes is a good biomarker for early AD.6464 Yang TT, Liu CG, Gao SC, Zhang Y, Wang PC. The Serum Exosome Derived MicroRNA-135a, -193b, and -384 Were Potential Alzheimer’s Disease Biomarkers. Biomed Environ Sci 2018;31(02): 87–96
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Small-nucleolar-RNAs |
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SNORD115 and SNORD116 |
- increased levels in plasma isolated EVs from AD patients in comparison to controls; enabled diferentiation between controls and AD with a 94.7%AUC.6666 Fitz NF, Wang J, Kamboh MI, Koldamova R, Lefterov I. Small nucleolar RNAs in plasma extracellular vesicles and their discriminatory power as diagnostic biomarkers of Alzheimer’s disease. Neurobiol Dis 2021;159:105481. Doi: 10.1016/j.nbd.2021.105481 https://doi.org/10.1016/j.nbd.2021.10548...
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Mitochondrial-RNAs |
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MT-ND1-6, MT-ND4L, MT-ATP6, MTATP8, MT-CYTB, MT-CO1, MT-CO2, MT-CO3 mRNAs, and MT-RNR1 rRNA |
- elevated levels in plasma isolated EVs from AD and MCI patients in comparison to controls.7272 Kim KM, Meng Q, Perez de Acha O, et al. Mitochondrial RNA in Alzheimer’s Disease Circulating Extracellular Vesicles. Front Cell Dev Biol 2020;8:581882. Doi: 10.3389/fcell.2020.581882 https://doi.org/10.3389/fcell.2020.58188...
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Lipids |
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Plasmalogen glycerophosphoethanolamine |
- increased levels in BDEVs isolated from frontal cortex tissue of AD patients in comparison to controls.7575 Su H, Rustam YH, Masters CL, et al. Characterization of brainderived extracellular vesicle lipids in Alzheimer’s disease. J Extracell Vesicles 2021;10(07):e12089. Doi: 10.1002/jev2.12089 https://doi.org/10.1002/jev2.12089...
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Polyunsaturated fatty acyl containing lipids |
- decreased levels in BDEVs isolated from frontal cortex tissue of AD patients in comparison to controls.7575 Su H, Rustam YH, Masters CL, et al. Characterization of brainderived extracellular vesicle lipids in Alzheimer’s disease. J Extracell Vesicles 2021;10(07):e12089. Doi: 10.1002/jev2.12089 https://doi.org/10.1002/jev2.12089...
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