Table 1. Summary of studies that specialized in or mentioned individuals with preclinical AD and used plasma Aβ as biomarkers.
| Samples | Diagnosis of Preclinical AD | Blood Biomarkers | Methods Used | Significance | Refs. |
|---|---|---|---|---|---|
| Converters, 339, with 570 plasma samples available; non-converters, 339 | 9.4±4.0 (range 0.2-20.7) years before converting to dementia; mostly pure clinical diagnosis, part was further supported by CSF analysis |
Aβ42, Aβ40, Aβ42/Aβ40 | INNO-BIA plasma Aβ forms kit, xMAP technology | No differences in the full sample or in subgroups defined according to sex and age | [86] |
| Converters, 53 (37 converted to AD-dementia, 11 to vascular dementia, 5 to other dementia); non-converters, 677 | 5-year follow-up, pure clinical diagnosis | Aβ42, Aβ40, Aβ42/Aβ40 | INNO-BIA plasma Aβ forms kit, xMAP technology | No differences between converters (to dementia or AD-dementia) and non-converters; baseline Aβ40 levels above the median had an increased risk of developing AD-dementia during the follow-up, even after adjustment for covariates (OR: 2.2) | [79] |
| Converters (HC to MCI/dementia, MCI to dementia), 26; non-converters (HC to HC), 119 | Base line and 36 months follow-up; clinical transition and supported by amyloid-PET | Aβ42, Aβ40, Aβ42/Aβ40, Aβx-42, Aβx-40, Aβx-42/Aβx-40 | INNO-BIA plasma Aβ forms kit, xMAP technology | Aβ42 and Aβ42/Aβ40 were decreased at baseline and at 18 months in the conversion group | [75] |
| HC, 189 | Amyloid-PET | Aβ42, Aβ40, Aβx-42, Aβx-40 | INNO-BIA plasma Aβ forms kit, xMAP technology | No relationships were observed between mean SUVR and Aβ | [85] |
| HC, numbers not clear | CSF analysis | Aβ42, Aβ40, Aβ42/Aβ40 | INNO-BIA plasma Aβ forms kit, xMAP technology | No differences between HC+ and HC- when stratified by CSF biomarkers | [87] |
| HC+, 28; HC-, 187 | Amyloid-PET | MPP-Aβ42, MPP-Aβ40, MPP-Aβ42/Aβ40 | INNO-BIA plasma Aβ forms kit, xMAP technology | MPP-Aβ42/Aβ40 was decreased in the HC+; MPP-Aβ40 was correlated with PET SUVR | [70] |
| HC, 167 | Amyloid-PET | Aβ42, Aβ40, Aβ42/Aβ40 | INNO-BIA plasma Aβ forms kit, xMAP technology | No relationships were observed between mean SUVR and Aβ (Perth site); only Aβ42/Aβ40 (Melbourne site) was correlated with SUVR | [71] |
| HC, 189 | CSF analysis | Aβ42/Aβ40 | Not mentioned | Pure Aβ42/Aβ40 predicted abnormal amyloid status with SEN 30.8%, SPE 71.0%; added Aβ42/Aβ40 not extra increased AUC of the base model (age plus APOE ε4) (from 0.74 to 0.76) | [99] |
| Converters, 64; non-converters, 394 | 14.8±4.9 (range 4.1-23.5) years before converting to dementia; pure clinical diagnosis | Aβ38, Aβ40, Aβ42, Aβ40/Aβ42 | ELISA | Lower levels of Aβ38 and Aβ42 were associated with increased risk of AD-dementia | [74] |
| HC+, 20-36; HC-, 42-52 | Base line and 18, 36, 54, 72 months follow-up; by amyloid-PET at the 18, 36, 54 months follow-up time point | Total Aβ42/Aβ40, free Aβ42/Aβ40, Aβ42/Aβ40 bound to plasma components | ELISA | Inverse associations of Aβ42/Aβ40 and PET SUVR both in cross-sectional and longitudinal analyses; total Aβ42/Aβ40 plus demographic covariates provided a median 0.81 positive predictive value of abnormal amyloid status | [88] |
| SCD, 200 | Amyloid-PET | Total and free plasma Aβ42, Aβ40, Aβ42/Aβ40 | ELISA | Total plasma Aβ42/Aβ40 was correlated with PET SUVR after controlling for age and APOE ε4 status; when cut-off at 0.08, SEN=83.3% and SPE=51.9% in identifying SCD+ | [97] |
| HC+, 5; HC-, 13 | Amyloid-PET | Total and free Aβ42/Aβ40 | ELISA | Total Aβ42/Aβ40 can predict abnormal amyloid status with 1.00 accuracy in the logistic regression model and had an AUC of 0.91 in the ROC curve model | [98] |
| HC-, 18; SCD-, 25 | CSF analysis | Aβ42 | Immunomagnetic reduction | Plasma Aβ42 was weakly positive correlated with CSF Aβ42 (R=0.186) | [94] |
| HC, 513 (SCD, 195; non-SCD, 318, or, HC+, 147; HC-, 366) | CSF analysis | Aβ42, Aβ40, Aβ42/Aβ40 | Elecsys immunoassays | Aβ42 and Aβ42/Aβ40 were lower in HC+; plasma Aβ42 and Aβ40 model can predict amyloid status with AUC about 0.77 | [96] |
| HC+, 74; HC-, 200; SCD+, 60; SCD-, 114 | CSF analysis; 125 HC and 103 SCD had amyloid-PET | Aβ42, Aβ40, Aβ42/Aβ40 | SIMOA | No statistical differences between HC and SCD; Aβ42 and Aβ42/Aβ40 were both correlated with their corresponding CSF Aβ isoforms in HC or SCD group; Aβ42/Aβ40 was correlated with SUVR in SCD group; Aβ42 and Aβ42/Aβ40 were both lower in HC+ or SCD+ group compared with HC- | [95] |
| SCD+, 73; SCD-, 203 | Amyloid-PET | Aβ42, Aβ40, Aβ42/Aβ40 | SIMOA | Aβ42 and Aβ42/Aβ40 were lower in SCD+; Aβ42 was negatively correlated with global/regional PET SUVR, predicted amyloid status with AUC 0.68, AUC of Aβ42/Aβ40 was 0.79 | [91] |
| SCD, 248 | CSF analysis; 69 had amyloid-PET | Aβ42, Aβ40, Aβ42/Aβ40, total-tau | SIMOA | Aβ42 and Aβ42/Aβ40 were both lower in SCD+, and positively associated with CSF Aβ42 levels and negatively associated with CSF total-tau and p-tau181; pure Aβ42/Aβ40 and Aβ42 both can predict CSF/PET-based abnormal amyloid status (AUC 66%-77%) and clinical progression (HR 2.31 and 1.74) | [90] |
| HC+, 32 (SCD, 23; non-SCD, 9); HC-, 63 (SCD, 49; non-SCD,14) | Amyloid-PET | Aβ42, Aβ40, Aβ42/Aβ40 | SIMOA | Aβ42/Aβ40 was lower in HC+ of both whole samples or SCD samples, not in non-SCD samples; Aβ42/Aβ40 additionally increased the predictive accuracy of base model (age plus APOE ε4) from 0.75 to 0.78 | [92] |
| Cohort 1: HC+, 66; HC-, 90. Cohort 2: HC+, 9; HC-, 48 | Amyloid-PET | APP669-711/Aβ42, Aβ42/Aβ40, Aβ composite score | Immunoprecipitation-mass spectrometry | Dichotomy by Aβ composite scores, the PET SUVR and PET status were both different between HC+ and HC- | [93] |
| HC+, 43; HC-, 115. A sub-cohort of 100 had at least 1 amyloid-PET >1.5 years following their baseline plasma sample | Amyloid-PET; mostly also supported by CSF analysis | Aβ42, Aβ40, Aβ42/Aβ40 | Immunoprecipitation-mass spectrometry | Aβ42/Aβ40 was lower in HC+, correlated with PET SUVR and CSF Aβ42/Aβ40, and can predict PET-based abnormal amyloid status at baseline (AUC 0.88); Aβ42/Aβ40 was lower in PET status converters to non-converters, individuals<0.1218 had a 15-fold increased risk of conversion | [64] |
Note: The number of participants and contents do not represent the total number and content of the original study. Abbreviations: AD, Alzheimer’s disease; Aβ, β-amyloid; CSF, cerebrospinal fluid; OR, odds ratio; HC, cognitively healthy controls; MCI, mild cognitive impairment; PET, positron emission tomography; SUVR, standardized uptake value ratio; MPP, mixture of protease inhibitors and phosphatase inhibitors; SEN, sensibility; SPE, specificity; AUC, area under curve; APOE, apolipoprotein E; ELISA, enzyme linked immunosorbent assay; ROC, receiver operating characteristic; SCD, subjective cognitive decline; SIMOA, single molecule array; HR, hazard ratio; p-tau181, tau phosphorylated at threonine 181; APP, Aβ precursor protein; ‘+’ means amyloid positive; ‘-’ means amyloid negative.