Table 1 Characteristics of experimental design for studies that examined sTREM2 in CSF and plasma
Study | Sample Type | Method of sTREM2 Detection | Main Finding (p-value) | sTREM2 (pg/ml), mean ± sd or median(IQR) | Study Cohort | Controls (CTR) | Diagnostic Parameters | Age (yrs) mean ± sd or Median(range) | Gender (percent female) | ApoE ε4+ carriers | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Criteria | Cognitive Testing | Other | ||||||||||
Gispert et al. (2016) [316] | CSF | ELISA | ↑ sTREM2 [CTR-MCI (0.01); PreAD-MCI (0.036); CTR-AD (0.044)] | Relat. to IS CTR: 400 ± 200 PreAD: 530 ± 390 MCI: 710 ± 420 AD: 620 ± 400 | PreAD (n = 19), MCI due to AD (n = 27), and mild AD (n = 23); all non-TREM2 variant carriers | Cognitively normal subjects defined by MMSE score > 27, CDR = 0, and negative AD CSF profilea (n = 45) | NIA-AA for AD and MCI due to AD groups | MMSE and CDR; PreAD had MMSE score > 27 and CDR = 0 | MRI; Positive AD CSF profile: Aβ42 (<500 pg/ml), t-tau (>450 pg/ml), and p-tau (>75 pg/ml) | CTR: 60.98 ± 6.83 PreAD: 68.53 ± 7.93 MCI: 70.30 ± 7.35 AD: 66.78 ± 9.75 | CTR: 63% PreAD:68% MCI: 55% AD: 69% | CTR: 15% PreAD:42% MCI: 52% AD: 48% |
Suárez-Calvet et al. (2016) [202] | CSF | ELISA | ↑ sTREM2 [CTR-MCI (0.002); AD-MCI (0.013); PreAD-MCI (0.062)] | Relat. to IS CTR: 470 ± 202 PreAD: 644 ± 410 MCI: 802 ± 380 AD: 725 ± 440 | PreAD (n = 63), MCI due to AD (n = 111), and AD (n = 200), from five centers | Asymptomatic cognitively normal subjects with a negative AD CSF profilea, determined across five centers (n = 150) | NIA-AA for each group | NR | Positive AD CSF profilea with cut-off values unique to each center (refer to [322]) | CTR: 62.4 ± 11 PreAD: 70.8 ± 11 MCI: 74.3 ± 9 AD: 73.8 ± 10 | CTR: 59% PreAD:60% MCI: 60% AD: 62% | CTR: 21% PreAD:58% MCI: 52% AD: 62% |
Suárez-Calvet et al. (2016) [12] | CSF | ELISA | ↑ sTREM2 [NC-MC (0.004)] | NC: 2824 ± 1292 MC: 3561 ± 1661 | Cases with ADAD (n = 127) from DIAN cohort | Noncarriers (n = 91) for ADAD-related mutations from DIAN cohort | Presence of ADAD mutation (PSEN1, PSEN2, or APP) assessed by DIAN | MMSE and CDR | AD CSF profile examined | NC: 39.5 ± 11 MC: 40.4 ± 11 | NC: 54% MC: 50% | NC: 34% MC: 28% |
↑ sTREM2 [MC with CDR = 0.5 (0.006); MC with CDR = 1 (0.044)] | No. of Subjects per CDR: CDR n 0 52 0.5 51 1 16 2 to 3 8 | No. of Subjects per CDR: CDR n 0 88 0.5 3 1 0 2 to 3 0 | ||||||||||
Heslegrave et al. (2016) [314] | CSF | Novel reaction monitoring assay with UPLC/TQ-S MS | ↑ sTREM2 [CTR-AD (0.0457)] | CTR: 195.6 (131.0–240.7) AD: 231.2 (172.5–305.4) | UK cohort: AD (n = 37) | Cognitively normal with negative AD CSF profilea (n = 22) | Revised IWG2 for AD | MMSE | Positive AD CSF profilea (Aβ42 < 550 pg/ml, t-tau >375 pg/ml, p-tau >52 pg/ml) | CTR: 69.2 ± 8.0 AD: 70.51 ± 7.5 | CTR: 45% AD: 53% | CTR: 33% AD: 67% |
↑ sTREM2 [CTR-AD (0.0312)] | CTR: 171 (153.5–241.5) AD: 230 (166.5–297.4) | Swedish cohort: AD (n = 24) | Cognitively normal subjects (n = 16) | NIA-AA for AD or MCI due to AD | MMSE | MRI or CT; Blood screening (unspecified) | CTR: 55.6 ± 9.7 AD: 64.3 ± 6.8 | CTR: 56% AD: 54% | CTR: 31% AD: 69% | |||
Kleinberger et al. (2014) [225] | CSF | ELISA | ↓ sTREM2 [CTR-AD (0.001)] | Relat. Values CTR: 0.381 (0.283–0.518) AD: 0.309 (0.178–0.436) | AD (n = 56), from AD-confirmed cases across six centers | Cognitively normal with negative AD CSF profilea (CSF: n = 88; plasma: n = 86) | NINCDS-ADRDA for probable AD | NR | Positive AD CSF profilea defined by the Mattsson et al. equation: [324] (Aβ42/p-tau)/(3.694 + 0.0105 x t-tau) | CTR: 60.7 ± 9.5 AD: 70.4 ± 8.9 | CTR: 63% AD: 68% | NR |
Plasma | ↔ sTREM2 [CTR-AD (0.872)] | Relat. Values CTR: 1.022 (0.675–1.864) AD: 0.998 (0.702–1.375) | AD (n = 51), from AD confirmed cases across six centers | CTR: 60.4 ± 9.5 AD: 70.7 ± 9.0 | CTR: 64% AD: 71% | NR | ||||||
Henjum et al. (2016) [203] | CSF | ELISA | ↔ sTREM2 [CTR-MCI (0.42); CTR-AD (0.17)] | CTR: 4400 (3000–5700) MCI: 4100 (2400–5900) AD: 4800 (3500–7100) | Norwegian cohort: AD (n = 29) or MCI due to AD (n = 21) | Cognitively normal subjects (n = 50) | DSM-IIIR for dementia; NINCDS-ADRDA for AD | MMSE | MRI or CT | CTR: 66 (50–86) MCI: 67 (55–75) AD: 68 (56–75) | CTR: 50% MCI: 57% AD: 45% | CTR: 0% MCI: 38% AD: 34.5% |
↔ sTREM2 [CTR-AD (0.76)] | CTR: 3200 (2800–5000) AD: 3800 (2600–5600) | Swedish cohort: AD (n = 25) | Cognitively normal with normal Aβ42 levels (>550 pg/ml) (n = 25) | NIA-AA for AD or MCI due to AD | MMSE | MRI or CT; Blood screening (unspecified) | CTR: 62 (43–80) AD: 79 (61–86) | CTR: 68% AD: 72% | CTR: 4% AD: 16% | |||
Piccio et al. (2016) [86] | CSF | ELISA | ↑ sTREM2 [CTR-AD (0.015)] | CTR: 1028 (244–2570) AD: 832 (163–2196) | Those with mainly mild AD, non-TREM2 variant carriers (CSF: n = 73; plasma: NR), from two centers | Cognitively normal subjects (CDR 0) and negative for AD CSF profilea (CSF: n = 107; plasma: NR) | NINCDS-ADRDA for probable AD | CDR | NR | CTR: 70.2 ± 8.5 AD: 76.6 ± 5.2 | CTR: 53% AD: 49% | CTR: 48% AD: 64% |
Plasma | ↔ sTREM2 [CTR-AD (0.74)] | CTR: 976 (65–2477) AD: 1019 (190–2546) | NR | NR | NR | |||||||