Table 2a:
Summary of ECM proteomic (P), glycomic (G), and glycoproteomic (GP) studies in Alzheimer’s disease using human samples over the last decade.
| Study Type | Brain Region/Sample Type |
Method | Major Findings | Dataset Availability |
Reference |
|---|---|---|---|---|---|
| Brain tissue | |||||
| P | Hippocampus, parietal cortex, cerebellum; AD n=4, controls n=4 for each region | RP LC-HCD-MS/MS, quantified by iTRAQ | -950 proteins identified; 31 differentially expressed -Tenascin-R decreased in abundance in AD |
Not publicly available | (Manavalan et al., 2013) |
| P | Synapses from hippocampus and primary motor cortex; AD n=6 and control n=6 | RP LC-HCD-MS/MS (DIA) | -2077 proteins identified; 68 differentially expressed -Versican decreased in abundance in AD |
Not publicly available | (R. Y. K. Chang et al., 2015) |
| P | Hippocampal subareas CA1 and subiculum, isolated using laser capture microdissection; n=40 with five to seven cases per Braak stage | RP LC-HCD-MS/MS validated using immuno-blotting and immuno-histochemistry | -3216 proteins identified; 372 differentially expressed -Increased abundance of tenascin-C, versican, laminin subunit beta-2, vimentin, galectin-1, annexin A5, and cathepsin D in AD. |
Not publicly available | (Hondius et al., 2016) |
| P | Amygdala, caudate nucleus, cerebellum, entorhinal cortex, inferior parietal lobule, middle frontal gyrus, superior temporal gyrus, thalamus, visual cortex from three individual brains (one with no tangles, one with intermediate tangles, one with severe tangles) | RP LC-HCD-MS/MS | -9735 proteins identified in at least one sample; 6256 quantified strong divergence -HAPLN4, Tenascin-A are increased in abundance in a region-specific manner |
Available in Proteome-Xchange, PRIDE partner repository; identifier PXD010603 | (McKetney et al., 2019) |
| G | Brain tissue (Frontal, parietal, occipital, and temporal cortices brain tissue), serum, and CSF AD n=6 and Control n=6 |
Glycoblotting and MALDI-TOF MS/MS analysis of enzymatically released N-glycans | -52 N-glycan structures identified -Bisecting-type and multiply branched glycoforms were increased significantly in AD CSF and serum compared to controls. |
Not publicly available | (Gizaw et al., 2016) |
| Cerebrospinal fluid | |||||
| P | Dorsolateral prefrontal cortex and CSF, n=453 | RP LC-HCD-MS/MS + TMT, protein co-expression analyzed using WGCNA | -5,668 proteins quantified, 13 protein coexpression modules identified -ECM module found to be correlated with pathological, cognitive, and functional measures |
Not publicly available | (Johnson et al., 2020) |
| G | CSF; AD n=24, MCI n=11, healthy control n=21 | Permethylated N-glycan MALDI TOF/TOF MS/MS analysis | -90 N-glycan structures identified -Decrease in sialylated N-glycans and increase in bisecting type N-glycans |
Not publicly available | (Palmigiano et al., 2016) |
| G | CSF; AD n=8 (4 male, 4 female), control n=8 (4 male, 4 female) | Reduced permethylated N-glycans RP LC-MS/MS | -Fucosylated and bisecting GlcNAc structures were higher in abundances in females with AD, while both females and males exhibited lower abundances of high-mannose structure | Not publicly available | (Cho et al., 2019) |
| G | CSF; control n=31, MCI n=25, AD n=27 | MALDI TOF/TOF, 2AB nano-LC-MS/MS analysis | -30 N-glycans identified in each sample pool -Increase in N-glycans carrying bisecting N-acetylglucosamine in AD |
Not publicly available | (Schedin-Weiss et al., 2020) |
| GP | CSF; AD n=16, control n=16 | RP LC-EThcD MS/MS | -285 N-glycoproteins identified -Altered glycosylation of alpha-1-antichymotrypsin and carnosinase CN1 -ECM structural constituent proteins and cell adhesion proteins enriched |
Available in Proteome-Xchange Consortium, MassIVE partner repository; identifier PXD02274 | (Z. Chen, Yu, et al., 2021) |
| GP | CSF; AD n=16, MCI n=16, control n=16 | RP LC-EThcD MS/MS | -308 O-glycopeptides from 110 glycoproteins identified -Decreased fucosylation and increasing endogenous O-glycosylation in AD |
Available in Mass Spectrometry Interactive Virtual Environment; deposit ID MSV000087160 | (Z. Chen, Wang, et al., 2021) |
| Other samples | |||||
| P | Extracellular vesicles; AD n=20, control n=18 | RP LC-HCD-MS/MS | -949 proteins quantified; 18 differentially expressed proteins -Annexin A5 increased in abundance in AD relative to controls |
Not publicly available | (Muraoka et al., 2020) |
| GP | Blood serum; AD n=136 and healthy controls without cognitive impairment n=183 | Serum glycoproteomics RP LC-MS/MS | -871 glycoproteins were identified, including 266 and 259 unique proteins in control and AD groups. 49 and 297 differentially abundant glycoproteins in AD -Increased abundance ECM glycoproteins-ADAM-TS8, coagulation factor X Decreased abundance-von Willebrand factor C domain-containing protein 2-like, -4.25-fold increase in ECM glycoproteins and ECM dysfunction as one of the altered pathways associated with AD |
Not publicly available | (Kerdsaeng et al., 2021) |