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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
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