Table 1.
Proteomic approaches, sample size and neuropsychological criteria for the groups used in the studies included
| No | Author and year | Proteomic approach | Controls samples | AD samples | Mean age (controls) | Mean age (AD) | Neuropsychological criteria | CSF biomarkers (control) | CSF biomarkers (AD) |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Whelan CD et al. (2019) [86] | Olink™ ProSeek immunoassay | 565 | 176 | 72 | 74.6 | NINCDS-ADRDA criteria, MMSE score and CSF biomarkers |
Mean Aβ42 [pg/ml(SD)]: 752(253) Mean Aβ40 [pg/ml(SD)]: 5847(2042) Aβ42/40 ratio - log2 transformed (SD): 2.05(0.17) Mean total tau [pg/ml(SD)]: 292(89) Mean phospho-tau [pg/ml(SD)]: 37(13) |
Mean Aβ42 [pg/ml(SD)]: 305(132) Mean Aβ40 [pg/ml(SD)]: 5470(2179) Aβ42/40 ratio - log2 transformed (SD): 2.9(0.29) Mean total tau [pg/ml(SD)]: 649(221) Mean phospho-tau [pg/ml(SD)]: 123(47) |
| 2 | Khoonsari et al. (2019) [87] | Nano LC-MS/MS (7 T hybrid LTQ FT MS) | 45 | 76 | 88 | 72 | NINCDS-ADRDA criteria, DSM-IV criteria, MMSE and CSF biomarkers |
Aβ42 ng/l (Median[range]): 676(337–1343) p-tau ng/l (Median[range]) 414 (202–1121) t-tau ng/l (Median[range]): 63 (29-122) |
Aβ42 ng/l (Median[range]): 405(160–1160) p-tau ng/l (Median[range]) 82 (28–220) t-tau ng/l (Median[range]): 617 (160–1720) |
| 3 | Sathe et al. [88] | High-Resolution MS, TMT multiplexing technology and targeted PRM analysis | 5 | 5 | 71 | 71.6 | CDR, MOCA, CSF biomarkers and NIA-AA criteria | Mean Aβ42 [pg/ml(SD)]: 1185.86(389.29) | Mean Aβ42 [pg/ml(SD)]: 402.11(189.62) |
| 4 | Duits et al. (2018) [89] | PRM | 40 | 40 | 64.5 | 64.6 | MMSE, clinical evaluation, and CSF biomarkers |
Mean Aβ42 [pg/ml(SD)]: 1086(161) Mean total tau [pg/ml(SD)]: 228(64) Mean phospho-tau [pg/ml(SD)]: 40(9) |
Mean Aβ42 [pg/ml(SD)]: 640(91) Mean total tau [pg/ml(SD)]: 740(433) Mean phospho-tau [pg/ml(SD)]: 94(47) |
| 5 | Dayon et al. (2018) [90] | RP LC-MS/MS | 48 | 72 | 66 | 73.7 | CDR, APOEa genotype and CSF biomarkers |
Mean Aβ42 [pg/ml(SD)]: 957.4(194) Mean total tau [pg/ml(SD)]: 221.5(82.9) Mean phospho-tau [pg/ml(SD)]: 45.9(13.3) Mean phospho-tau (SD)/Aβ42: 0.049(0.015) |
Mean Aβ42 [pg/ml(SD)]: 774(281.5) Mean total tau [pg/ml(SD)]: 471.1(316.6) Mean phospho-tau [pg/ml(SD)]: 72.7(40.9) Mean phospho-tau (SD)/Aβ42: 0.114(0.097) |
| 6 | Brinkmalm et al. (2018) [14] | PRM-MS analysis and previously nanoflow LC-MS/MS | 15 | 10 | 64.9 | 62.7 | Clinical evaluation, computer tomography (CT) scan and CSF Aβ42 | Mean Aβ42 [pg/ml(SD)]: 877.2(206.3) | Aβ42 < 400 pg/ml;Mean Aβ42 [pg/ml(SD)]: 275.4(106.8) |
| 7 | Skillbäck et al. (2017) [45] | Quantification-driven proteomic | 40 | 40 | 64.5 | 64 | NIA and IWG-2 criteria, CSF biomarkers and MMSE |
Information extracted from graphs: Mean Aβ42 [pg/ml]: 950 Mean total tau [pg/ml]: 260 Mean phospho- tau [pg/ml]: 55 |
Information extracted from graphs: Mean Aβ42 [pg/ml]: 450 Mean total tau [pg/ml]: 600 Mean phospho- tau [pg/ml]: 85 |
| 8 | Wang et al. (2016) [46] | LC-MS/MS and lectin-enrichment chromatography | 4 | 4 | 74 | 75.7 | Neuropsychological tests | NI | |
| 9 | Paterson et al. (2016) [91] | Targeted proteomics: MRM-based triple quadrupole mass spectral assay | 36 | 46 | 58.5 | 62.9 | APOE# genotype and CSF biomarkers |
Mean Aβ42 [pg/ml(SD)]: 960(291) Mean total tau (range): 234.5(174.5–315.5) Mean phospho-tau [pg/ml(SD)]: 35.5(13.2) Mean phospho-tau (range)/Aβ42: 0.25(0.19-0.33) |
Mean Aβ42 [pg/ml(SD)]: 408(2168) Mean total tau (range): 947(760–1196-315.5) Mean phospho-tau [pg/ml(SD)]: 107.5(38.12) Mean phospho-tau (range)/Aβ42: 2.5(1.8-4.1) |
| 10 | Remnestal et al. (2016) [92] | Suspension bead array: HPA antibodies targeting the 280 proteins | 38 | 72 | 58 | 77.4 | NINCDS-ADRDA criteria and CSF biomarkers |
Mean Aβ42 [pg/ml(range)]: 706(559-1192) Mean total tau (range): 308(171-399) Mean phospho-tau (range): 47(29-60) |
Group AD1: Mean Aβ42 [pg/ml(range)]: 350(160-950) Mean total tau (range): 600(210–2430) Mean phospho-tau (range): 78(34–282)Group AD2: Mean Aβ42 [pg/ml(range)]: 453(260–639) Mean total tau (range): 834(190–3178) Mean phospho-tau (range): 86(59–179) |
| 11 | Khoonsari et al. (2016) [16] | RP nano LC- MS/MS andantibody suspension bead arrrays | 10 | 10 | 88.2 | 79.4 | Clinical evaluation, CSF biomarkers and MMSE | NI |
Mean Aβ42 [ng/l]: 420.1 Mean total tau [ng/l]: 652.1 Mean phospho-tau [ng/l]: 132.2 |
| 12 | Domenico et al. (2016) [93]** | 2-DE - WB - MS (2-DE gel/carbonyl immunoblot) | 6 | 6 | NI | NI | NINCDS-ADRDA criteria, neuropsychological test and APOE# genotype | NI | |
| 13 | Heywood et al. (2015) [94] | Label-free proteomic analyses (2-DE LC-MS) and Targeted proteomics: MRM-based triple quadrupole mass spectral assay | 15 | 16 | 61 | 68.1 | CSF biomarkers |
Mean Aβ42 [pg/ml(SD)]: 905.41(237) Mean total tau [pg/ml(SD)]:136.58(162) Mean phospho-tau [pg/ml(SD)]: 19.33(11.11) |
Mean Aβ42 [pg/ml(SD)]: 503.68(165.8) Mean total tau [pg/ml(SD)]:733.77(481.25) Mean phospho-tau [pg/ml(SD)]: 93.38(31.55) |
| 14 | Hendrickson et al. (2015) [20] | RP nano-HPLC coupled to an LTQ-FTMS hybrid mass spectrometer. SRM-MS | 30 | 30 | 69 | 70 | NINCDS-ADRDA criteria and APOE# genotype | NI | |
| 15 | Spellman et al. (2015) [95] | LC/MRM-MS | 85 | 66 | 75.6 | 75 | APOE# genotype, CSF biomarkers and MMSE |
Mean Aβ42 [SD]: 207.8(56.26) Mean phospho-tau (SD): 24.19(12.02) |
Mean Aβ42 [SD]: 141.12(37.39) Mean phospho-tau (SD): 41.95(20.6) |
| 16 | Hölttä et al. (2015) [15] | TMT, LC−ESI MS, LC−MALDI MS | 8 | 8 | 65 | 77 | DSM-IIIRand NINCDS-ADRDA criteria |
Mean Aβ42 [pg/ml(range)]: 700(545–817) Mean total tau (range): 405(330–523) |
Mean Aβ42 [pg/ml(range)]: 235(210–298) Mean total tau (range): 800(717–925) |
| 17 | Leung et al. (2015) [96] | MAP-RBM platform (XMAP Luminex platform) /ELISA | 325 | 344 | 71.7 | 74 | MMSE, CDR, NINDS-ADRDA criteria and CSF biomarkers | Aβ42 > 192 pg/ml | Aβ42 < 192 pg/ml |
| 18 | Khan et al. (2015) [97]** | XMAP Luminex platform | 88 | 65 | 75.8 | 74.6 | APOE# genotype, CSF biomarkers, and MMSE |
Mean Aβ42 [(SD)]: 205.7(57.2) Mean total tau (SD):69.2(27.9) Mean phospho-tau (SD): 24.9(13.2) |
Mean Aβ42 [(SD)]: 140.4(35.3) Mean total tau (SD):125.9(60.3) Mean phospho-tau (SD): 42.2(20.7) |
| 19 | Oláh et al. (2015) [98] | Master Antibody Microarray and WB | 25 | 25 | 74.5 | 72 | Clinial evaluation, NINCDS-ADRDA criteria, APOE# genotype and CSF biomarkers |
Mean Aβ42 [pg/ml(SD)]: 794(20) Mean total tau [pg/ml(SD)]: 341(171) Mean phospho-tau [pg/ml(SD)]: 23(2) |
Aβ42 < 500 pg/ml total tau >600 pg/ml phospho-tau>60 pg/ml |
| 20 | Alzate et al. (2014) [99] | MS and MS/MS and 2-DE multiplexed WB | 7 | 11 | AR: 62.8 to 81.5 | AR: 62.8 to 81.5 | APOE# genotype | NI | |
| 21 | Wildsmith et al. (2014)[100] | LC-MS/MS, Targeted LC-MRM and ELISA | 10 | 45 | 68.5 | 77.5 | MMSE and CSF biomarkers |
Information extracted from graphs: Mean Aβ42 [pg/ml]: 650 Mean total tau [pg/ml]: 60 Mean phospho- tau [pg/ml]: 25 |
Information extracted from graphs: Mean Aβ42 [pg/ml]: 400 Mean total tau [pg/ml]: 150Mean phospho- tau [pg/ml]: 60 |
| 22 | Chakrabarti et al. (2014) [101] | 2-DE, MALDI MS Analysis and co-immunoprecipitation | 11 | 11 | 67 | 71 | NINCDS-ADRDA criteria, DSM-IV criteria, MMSE, CDR and other tests | NI | |
| 23 | Choi et al. (2013) [49]** | Nano LC-MS/MS and nano LC-MRM/MS and ELISA | 3 | 3 | NI | NI | Confirmed by autopsy | NI | |
| 24 | Wijte et al. (2012) [102] | MALDI TOF/TOF MS | 20 | 20 | 77.7 | 75.95 | Postmortem neuropathological evaluation | NI | |
| 25 | Ringman et al. (2012) [103] | MS/MS, 2-DE LC/MS | 5 | 4 | 37.6 | 34.2 | CDR and FAD mutation carriers (MCs) and related noncarrieres (NCs)Π. APOE# genotype and CSF biomarkers |
Mean Aβ42 [pg/ml(SD)]: 618.4(100.1) Mean total tau [pg/ml(SD)]: 50.5(9.4) Mean phospho-tau [pg/ml(SD)]: 24.6(9.2) |
Mean Aβ42 [pg/ml(SD)]: 277.1(162.9) Mean total tau [pg/ml(SD)]: 140(59.9) Mean phospho-tau [pg/ml(SD)]: 67(29) |
| 26 | Manral et al. (2012) [104] | 2-DE and Nano LC-ESI-Q-TOF MS/MS system | 8 | 8 | 60.7 | 62.6 | NINCDS-ADRDA criteria, MMSE score and MRI | NI | |
| 27 | Vafadar-Isfahani et al. (2012) [105] | nLC-MALDI-TOF MS/MS and MALDI TOF/TOF MS | 23 | 33 | NI | NI | NINCDS-ADRDA criteria, DSM-IV and MMSE and clinical evaluation |
Information extracted from graphs: Mean Aβ42 [pg/ml]: 440 Mean Aβ40 [pg/ml]: 5000 Mean total tau [pg/ml]: 500 |
Information extracted from graphs: Mean Aβ42 [pg/ml]: 190 Mean Aβ40 [pg/ml]: 3900 Mean total tau [pg/ml]: 2000 |
| 28 | Jahn et al. (2011) [44] | CE-MS and MS/MS | 17 | 34 | 58.9 | 69 | NINCDS-ADRDA criteria, CSF biomarkers and MMSE score | NI |
Mean Aβ42 [pg/ml]: 300.91 Mean total tau [pg/ml]: 541.21 Mean phospho-tau [pg/ml]: 81.84 |
| 29 | Craig-Schapiro et al. (2011) [106]** | ELISA (targeted) | 242 | 28+63 | 71.6 | 76.8 | NINCDS-ADRDA criteria and CDR | NI | |
| 30 | Perrin et al. (2011) [50] | 2-DE DIGE / nano- LC-MS/MS | 198 | 29 | 71 | 76.5 | CDR, MMSE score and CSF biomarkers |
Mean Aβ42 [pg/ml(SD)]: 605(240) Mean total tau [pg/ml(SD)]: 304(161) Mean phospho-tau [pg/ml(SD)]: 55(25) |
Mean Aβ42 [pg/ml(SD)]: 351(118) Mean total tau [pg/ml(SD)]: 552(263) Mean phospho-tau [pg/ml(SD)]: 77(38) |
| 31 | Hu et al. (2010) [107]** | XMAP Luminex platform | 33 | 66 | NI | NI | MMSE, CSF biomarkers and confirmed by autopsy | NI | |
| 32 | Maarouf et al. (2009) [108] | 2-DE DIGE and MS | 43 | 47 | 84 | 79 | APOE# genotype, CERAD and the NIA-Reagan Institute | NI | |
| 33 | Yin et al. (2009) [109] | 1-DE and LC–MS/MS | 6 | 5 | 55.3 | 71 | NINCDS-ADRDA criteria | NI | |
| 34 | Zhang et al. (2008) [110] | Immunobead-based multiplex assays | 95 | 48 | 63 | 70 | Clinical evaluation | NI | |
| 35 | Jung et al. (2008) [66] | 2-DE, DE-MALDI-TOF MS | 30 | 27 | 73.2 | 77.7 | NINCDS-ADRDA criteria and CDR | NI | |
| 36 | Simonsen et al. (2007) [111] | MS | 32 | 85 | 68.3 | 69.15 | NINCDS-ADRDA criteria, MMSE score and clinical evaluation | NI | |
| 37 | Hu et al. (2007) [112]** | 2-DE DIGE, MS/MS and ELISA | 55 | 19 | NI | NI | CSF biomarkers, CDR and clinical evaluation |
Information extracted from graphs: Mean Aβ42 (range): 1(0–2) Mean total tau (range): 0.9(0–5)Mean phospho- tau (range): 0.8(0–5) |
Information extracted from graphs: Mean Aβ42 (range): 0.6(0–2) Mean total tau (range): 1.9(0–5)Mean phospho- tau (range): 1.1(0–5) |
| 38 | Korolainen et al. (2007) [113] | 2-DE and Nano LC-MS/MS | 8 | 11 | 64.7 | 73.54 | APOE# genotype, NINCDS-ADRDA criteria and MMSE score | NI | |
| 39 | Finehout et al. (2007) [114] | 2-DE and TOF/TOF MS | 12 | 44 | NI | NI | Postmortem confirmation | NI | |
| 40 | Simonsen et al. (2008) [115] | SELDI-TOF MS | 72 | 95 | 73.1 | 72.5 | NINCDS-ADRDA criteria, MMSE score and CSF biomarkers |
Group C1: Mean Aβ42 [pg/ml(SD)]: 876(209.2) Mean total tau (SD): 295.8 (153.6) Group C2: Mean Aβ42 [pg/ml(SD)]: 748.9(155.3) Mean total tau (SD): 332.9 (158.7) |
Group AD1: Mean Aβ42 [pg/ml(SD)]: 524.6(170.1) Mean total tau (SD): 739.1 (300.9) Group AD2: Mean Aβ42 [pg/ml(SD)]: 464(187.7) Mean total tau (SD): 657.7 (339.4) |
| 41 | Castaño et al. (2006) [116] | 2-DE and MALDI-TOF MS | 43 | 43 | 81 | 81 | Clinical diagnosis, Braak stages, and CERAD | NI | |
| 42 | Abdi et al. (2006) [52] | iTRAQ labeling and 2-DE LC, MS/MS and WB | 10 | 10 | 67 | 72 | MMSE, CDR, NINDS-ADRDA criteria and other test | NI | |
| 43 | Selle et al. (2005) [117] | MALDI-TOF-MS | 102 | 140 | 62.5 | 71 | ICD-10, NINCDS-ADRDA criteria, DSM-IV and MMSE | NI | |
| 44 | Zhang et al. (2005) [118]** | LC-MS ICAT | 20 | 32 | 70.5 | 71 | MMSE and CDR | NI | |
| 45 | Puchades et al. (2003) [68] | 2-DE and MALDI-TOF MS | 7 | 7 | 66 | 80 | NINCDS-ADRDA criteria and MMSE score | NI | |
| 46 | Carrette et al. (2003) [119] | SELDI-TOF MS using SAX2 Protein-chip arrays | 10 | 19 | 78 | 75 | NINCDS-ADRDA criteria | NI | |
| 47 | Davidsson et al. (2002) [120] | 2-DE, SYPRO Ruby staining and MS | 12 | 15 | 67.3 | 77.2 | NINCDS-ADRDA criteria and MMSE score | NI | |
| Total samples (Control) | Total samples (AD) | Average age (Control) | Average age (AD) | ||||||
| 2562 | 2022 | 70 | 73 | ||||||
ESI electrospray ionization, MRM multiple reaction monitoring, PRM parallel reaction monitoring, MS mass spectrometry, TMT tandem mass tag, RP-LC MS/MS reversed-phase LC-MS/MS, SRM reaction monitoring, CE-MS capillary electrophoresis mass spectrometry, SELDI-TOF-MS surface enhanced laser desorption/ionization time-of-flight mass spectrometry, WB Western Blot, AR age range, NI not information, CDR Clinical dementia rating scale, MOCA Montreal cognitive assessment, NINCDS-ADRDA National Institute of Neurological and Communicative Disorders and Stroke and the AD and Related Disorders Association, MMSE Mini-menta state exam, DSM Diagnostic and Statistical, FAD familial Alzheimer Disease, CERAD Consortium to Establish a Registry for Alzheimer’s Disease, ICD-10 10th revision of the International Statistical Classification of Diseases and Related Health Problems, IWG-2 International Working Group-2 criteria
#Studies based on APOE genotype
ΠStudy based on PSEN1 and APP mutations (this study was not considered to calculate the average age)
** Qualitative and not quantitative data