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Table 1 Characteristics of experimental design for studies that examined sTREM2 in CSF and plasma

From: TREM2 in Neurodegenerative Diseases

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

  1. 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]
  2. 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