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 |
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|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 |
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| 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% |
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| 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% |
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| 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 | |||||||
Abbreviations: AD Alzheimer’s disease, mild cognitive impairment [313], CSF cerebrospinal fluid, Aβ42 amyloid-β 1–42, p-tau Phosphorylated tau, t-tau total tau, IS internal standard, enzyme-linked immunosorbent assay [228], UPLC/TQ-S MS Tandem Quadrupole Mass Spectrometry, NC noncarriers, MC mutation carriers, ADAD autosomal dominant AD, NR not reported, PSEN presenilin, APP amyloid precursor protein, PreAD Preclinical AD, DSM Diagnostic and Statistical Manual of Mental Disorders, NIA-AA National Institute on Aging--Alzheimer’s Association, NINCDS-ADRDA National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association, IWG2 International Working Group, CDR clinical dementia rating, MMSE mini-mental state examination, MRI magnetic resonance imaging, computed tomography, Dominantly Inherited Alzheimer Network [268]
aThe ‘AD CSF profile’ consists of high t-tau and p-tau, and low Aβ42 levels in CSF; cut-off values are specified for each study. Under main finding, the results are presented as significantly elevated (↑), significantly reduced (↓), or non-significant differences (↔) in sTREM2