Table 1.
Studies included in NeuroPro
| Reference | Brain region(s) | AD stage(s) | Tissue fraction | Lysis and digestion | DEPs included in NeuroPro | Statistical approach |
|---|---|---|---|---|---|---|
| Bulk Tissue Homogenate | ||||||
| Andreev et al. (2012)8 | Temporal cortex | Control, AD | n/a | 8 M urea lysis. Trypsin digestion | 188 | FDR <5% |
| Astillero-Lopez et al. (2022)16 | Entorhinal cortex | Control, AD | n/a | RIPA buffer lysis. Trypsin digestion | 399 | FC >1.5 and p < 0.05 |
| Bai et al. (2020)26 | Frontal cortex | Control, preclinical AD, MCI, AD | n/a | 8 M urea lysis. Lys-C and trypsin digestion | 20 | FC >1.5 and p < 0.05 |
| Carlyle et al. (2021)33 | Parietal cortex | Control, preclinical AD, AD | Synaptic fraction | 3% SDS lysis. Lys-C and trypsin digestion | 167 | FDR <5% |
| Dai et al. (2018)17 | Frontal cortex | Control, AD | n/a | 8 M urea lysis. Lys-C and trypsin digestion | 100 | FC >1.5 and p < 0.05 |
| Donovan et al. (2012)30 | Frontal cortex | Control, AD | Membrane fraction | 8 M urea lysis of insoluble membrane-enriched fraction. Lys-C and trypsin digestion | 9 | FC >1.5 and p < 0.05 |
| Hales et al. (2016)31 | Frontal cortex | Control, preclinical AD, MCI, AD | Insoluble fraction | 8 M urea lysis of sarkosyl-insoluble fraction. In-gel trypsin digestion | 308 | FC >1.5 and p < 0.05 |
| Haytural et al. (2020)25 | Hippocampus | Control, AD | Specific region: Molecular layer of the dentate gyrus | Laser capture microdissection of specific region. 4% SDS lysis. Lys-C and trypsin digestion | 65 | FDR <5% |
| Higginbotham et al. (2020)4 | Frontal cortex | Control, AD | n/a |
8 M urea lysis. Lys-C and trypsin digestion |
102 | FC >1.5 and p < 0.05 |
| Ho Kim et al. (2015)12 | Hippocampus | Control, AD | Specific region: CA4 and dentate gyrus | Manual dissection of specific region. Unreported lysis. Trypsin digestion. | 103 | FDR <5% |
| Hondius et al. (2016)11 | Hippocampus | Control, AD | Specific region: CA1 and subiculum | Laser capture microdissection of specific region. M-PER lysis buffer plus SDS. In-gel trypsin digestion | 264 | FDR <5% |
| Johnson et al. (2018)15 | Frontal cortex | Control, preclinical AD, AD | n/a |
8 M urea lysis. Lys-C digestion |
841 | ANOVA and Tukey’s post hoc p < 0.05 |
| Johnson et al. (2020)14 | Frontal cortex | Control, preclinical AD, AD | n/a |
8 M urea lysis. Lys-C and trypsin digestion |
1081 | ANOVA and Tukey’s post hoc p < 0.05 |
| Johnson et al. (2022)2 | Frontal cortex | Control, preclinical AD, AD | n/a |
8 M urea lysis. Lys-C and trypsin digestion |
3493 | ANOVA and Holm post hoc p < 0.05 |
| Li et al. (2021)21 | Occipital cortex | Control, preclinical AD, AD | Soluble fraction; dispersible fraction; SDS- fraction; formic acid fraction. | Fractionation into soluble, dispersible, SDS-soluble and formic acid soluble fractions. Trypsin digestion. | 30 | Kruskal–Wallis H- test p < 0.05 |
| Manavalan et al. (2013)10 | Hippocampus, Cerebellum | Control, AD | n/a | 2% SDS lysis. In-gel trypsin digestion | 12 | FC >1.5 and p < 0.05 |
| McKetney et al. (2019)19 | Entorhinal cortex | Control, AD | n/a | 6 M guanidine lysis. Trypsin digestion. | 130 | FC >1.5 and p < 0.05 |
| Mendonca et al. (2019)28 | Entorhinal cortex, Parahippocampal cortex, Frontal cortex, Temporal cortex | Control, MCI, AD | n/a | 7 M urea lysis. Trypsin digestion. | 938 | FC >1.5 and p < 0.05 |
| Muraoka et al. (2020)32 | Frontal cortex | Control, AD | Extracellular vesicle fraction | Fractionation into extracellular vesicles. Sonication lysis. Trypsin digestion | 95 | FC >1.5 and p < 0.05 |
| Musunuri et al. (2014)9 | Temporal cortex | Control, AD | n/a | 1% β-octyl glucopyranoside lysis. Trypsin digestion | 28 | FC >1.5 and p < 0.05 |
| Ojo et al. (2021a)35 | Frontal cortex | Control, AD | Blood vessel-enriched fraction | Dextran-based cerebrovascular enrichment. 2% lithium dodecyl sulphate lysis. Trysin digestion. | 33 | FC >1.5 and p < 0.05 |
| Ojo et al. (2021b)34 | Frontal cortex | Control, AD | Blood vessel-enriched fraction | Dextran-based cerebrovascular enrichment. 2% lithium dodecyl sulphate lysis. Trypsin digestion. | 118 | FC >1.5 and p < 0.05 |
| Pearson et al. (2020)18 | Ventricle | Control, AD | Membrane and cytosolic fraction | Centrifugation based fractionation. Non-detergent lysis. Trypsin digestion. | 25 | FDR <5% |
| Ping et al. (2020)23 | Frontal cortex | Control, preclinical AD, AD | n/a | 8 M urea lysis. Lys-C and trypsin digestion | 103 | FC >1.5 and p < 0.05 |
| Seyfried et al. (2017)3 | Frontal cortex, Precuneus | Control, preclinical AD, AD | n/a | 8 M urea lysis. Lys-C and trypsin digestion | 937 | ANOVA and Tukey’s post hoc p < 0.05 |
| Stepler et al. (2020)24 | Hippocampus, Parietal cortex | Control, AD | n/a | 8 M urea lysis. Lys-C and trypsin digestion | 81 | FC >1.5 and p < 0.05 |
| Sweet et al. (2016)13 | Entorhinal cortex | Control, AD | n/a | 2% SDS lysis. In-gel trypsin digestion | 103 | FDR <5% |
| Wang et al. (2020b)80 | Frontal cortex | Control, AD | n/a | 8 M urea lysis. Lys-C and trypsin digestion | 150 | FDR <5% |
| Wingo et al. (2020)20 | Frontal cortex | Control, AD | n/a | 8 M urea lysis. Lys-C and trypsin digestion | 856 | FDR <5% |
| Xu et al. (2019)27 | Hippocampus, Entorhinal cortex, Cingulate gyrus, Motor cortex, Sensory cortex, Cerebellum | Control, AD | n/a | 0.1% SDS lysis. Trypsin digestion. | 2058 | FDR <5% |
| Zellner et al. (2022)42 | Parietal cortex | Control, AD | Blood vessel-enriched fraction | Ficoll-based extraction of blood vessels. 4% SDS lysis. Trypsin digestion. | 379 | FC >1.5 and p < 0.05 |
| Zhang et al. (2018)29 | Frontal cortex | Control, AD | n/a | 4% SDS lysis. Trypsin digestion. | 269 | FDR <5% |
| Amyloid plaques | ||||||
| Drummond et al. (2017)38 | Hippocampus | AD | Plaques | Laser capture microdissection of amyloid plaques visualised using a combination of 4G8 and 6E10 antibodies. Formic acid lysis. Trypsin digestion. | 1459 | In plaques in >3 cases |
| Drummond et al. (2022)36 | Hippocampus | AD | Plaques | Laser capture microdissection of amyloid plaques visualised using a combination of 4G8 and 6E10 antibodies. Formic acid lysis. Trypsin digestion. | 2114 | FC >1.5 in plaques vs non-plaques |
| Liao et al. (2004)39 | Frontal cortex | AD | Plaques | Laser capture microdissection of amyloid plaques visualised using Thioflavin-S. 2% SDS lysis. In-gel trypsin digestion. | 22 | FC >1.5 in plaques vs non-plaques |
| Xiong et al. (2019)40 | Hippocampus | AD | Plaques | Laser capture microdissection of amyloid plaques visualised using Amylo-Glo. 8 M urea lysis. Trypsin digestion. | 139 | FC >1.5 in plaques vs non-plaques |
| Neurofibrillary tangles | ||||||
| Drummond et al. (2020)37 | Hippocampus | AD | Tangles | Laser capture microdissection of tangles visualised using AT8 antibody. Formic acid lysis. Trypsin digestion. | 542 | In NFTs in >3 cases |
| Hondius et al. (2021)41 | Hippocampus | AD | Tangles | Laser capture microdissection of tangles visualised using AT8 antibody. M-PER lysis buffer plus SDS. In-gel trypsin digestion. | 112 | FC >1.5 in NFTs vs control neurons |
| Cerebral amyloid angiopathy | ||||||
| Zellner et al. (2022)42 | Parietal cortex | Control, AD | CAA-containing blood vessels | Ficoll-based extraction of CAA-containing blood vessels. 4% SDS lysis. Trypsin digestion. | 246 | P < 0.05 and FC >1.5 AD vs control |
AD stages refer to cognitively normal controls (’controls’); preclinical AD, mild cognitive impairment (’MCI’) and advanced AD (’AD’). Differentially Expressed Proteins (’DEPs’) shows the total number of all DEPs included in NeuroPro from each study (sum of DEPs from all AD stages and all brain regions). The statistical approach shows the stringency criteria that was used to define DEPs for each study. All t-tests were two-sided.