Skip to main content

Plasma Aβ biomarker for early diagnosis and prognosis of Alzheimer’s disease – a systematic review

Svend Ubbe Ebbesen1, Peter Høgh2, 3 & Ivan Zibrandtsen4

10. maj 2023
22 min.


Plasma Aβ biomarker for early diagnosis and prognosis of Alzheimer’s disease

Key Points

Key messages from the paper

Premorbid pathophysiological changes in Alzheimer’s disease (AD) precede symptom onset by decades [1-3]. The amyloid cascade hypothesis states that the earliest pathology and hallmark of AD is beta amyloid plaques (Aβ) in the brain [4]. The inter-neuronal pathological change is thought to induce the intra-neuronal tau pathology of tau fibrils. These events induce additional inflammation leading to synaptic dysfunction and ultimately dementia [5, 6].

Aβ originates from cleavage of the amyloid precursor protein, which is a transmembrane protein partially embedded in the plasma membrane [7, 8]. Aβ is denoted by a number referring to the number of amino acids that the isoform consists of. How exactly Aβ is distributed from the brain to the blood stream is not completely understood. However, it seems increasingly evident that Aβ is cleared into the plasma through cerebrospinal fluid (CSF) or via the blood-brain barrier [9].

CSF biomarker analyses and amyloid PET (aPET) may be used to track AD pathology and thus have diagnostic applicability [10]. However, CSF analysis is a time-consuming and invasive procedure and an aPET is expensive and less available outside academic hospitals [11]. Diagnosing solely based on clinical assessments is less accurate so a cost-effective plasma biomarker has been extensively sought after.

CSF Aβ42 levels have been robustly shown to be lower in AD patients than in cognitively unimpaired elderly [12]. The pathophysiology of this phenomenon is thought to be that Aβ42 is sequestered in the insoluble plaques of the brain in AD, which lowers the amount secreted to the CSF [13]. Indeed, it was shown that antemortem CSF Aβ42 correlates inversely with the amount of senile amyloid plaques measured both postmortem [14] and antemortem [15] (by aPET).

Many studies have shown that CSF Aβ40 (which is found at around ten times higher concentrations than CSF Aβ42 [16, 17]) exhibits only minor or no changes in AD [12], whereas the CSF Aβ42/40 ratio was proven to be superior in identifying AD compared with isolated CSF Aβ42 [18-20]. It is hypothesised that the CSF Aβ42/40 ratio lessens the interindividual variance as CSF Aβ40 is seen as a proxy for total Aβ, which may differ between individuals [21].

This systematic review investigates the biomarker potential of plasma Aβ. The focus is on Aβ42, Aβ40 and the Aβ42/40 ratio and their respective association with already established biomarkers of AD pathology; aPET positivity and CSF Aβ levels.


PubMed was searched for articles for the systematic review using the terms listed in Table 1. The publication types of Reviews and Clinical Trials were excluded and only articles published from 2017-2021 with human species in English were included. This search yielded 185 articles.

After excluding articles about other biomarkers than Aβ and articles with no relevance to Aβ in plasma, 50 articles remained. The methods used in these 50 articles were reviewed and only articles in which the population of interest had undergone either lumbar puncture for the biomarker analyses of CSF or aPET (or both) were included in the current systematic review. This procedure left 14 articles for review. Apart from these 14 articles, three more were added by the reviewers during peer review, yielding a total of 17 included articles.

The PubMed search was conducted according to the PRISMA guidelines and a flow diagram including further exclusion reasons is presented in Figure 1.

A meta-analysis was conducted including the studies reporting correlation coefficients describing the relationship between the Aβ42/40 ratio in plasma and the Aβ42/40 ratio in CSF or aPET. The meta-analysis was conducted in R version 4.2.1 using the meta package.


Plasma Aβ as an amyloid PET surrogate

Increased standardised uptake value ratio of the Aβ binding isotope demonstrated by aPET is a gold standard biomarker of AD [10]. Several studies have investigated the relationship between plasma Aβ and aPET.

Plasma Aβ42 and Aβ40

It has been proposed that abnormal levels of isolated Aβ42 in plasma is the first detectable biomarker in AD [24]. Multiple studies have investigated both Aβ42 in CSF and plasma, and beta amyloid in senile plaques with aPET. In a study by Verberk et al., no relation was found between plasma Aβ40 and aPET; however, plasma Aβ42 levels were shown to be lowered in subjective cognitive decline (SCD: Subjects with a “self-perceived decline in any cognitive domain over time” [25]) patients (n = 69) with positive aPET compared with patients with negative aPET [26]. Contradicting this, in a study by Park et al. where plasma was treated with a mixture of phosphatase inhibitors and protease inhibitors (MPP-treated), MPP-treated plasma Aβ42 and Aβ40 levels were found to be higher in mild cognitive impairment (MCI: Subjects meeting the following criteria: a) memory complaints by oneself, an informant or a clinician; b) objective memory impairment; c) having largely intact functional activities; d) no dementia; e) No other cognitive disorder or medical condition affecting mental status [27]) patients with positive aPET scans compared with MCI patients with negative aPET scans [27]. Furthermore, aPET-positive subjects (consisting of cognitively normal subjects, MCI patients and AD patients) had significantly higher levels of MPP-treated plasma Aβ40 [27]. Other studies have found no association between Aβ42 and aPET [28-30].

Plasma Aβ42/40 ratio

Six studies conducted a correlation analysis between aPET positivity and low plasma Aβ42/40 ratio. The results of a meta-analysis of the correlation coefficients is shown in Figure 2, giving a random-effects model estimate of r = –0.48 (95% confidence interval (CI): –0.65-–0.31) with an  of 90%. The substantial heterogeneity is underscored by the fact that point estimates differ much between studies with Doecke et al. and Schindler et al. reporting moderately negative correlations below –0.5 and de Rojas et al. and Park et al. reporting small negative correlations. Pérez-Grijalba et al. had the smallest sample of only 59 cases and thus reported wide CIs. The overall sample is too small for analysis for a possible publication bias.

In cognitively normal people, Schindler et al. found that aPET-positive subjects had a significantly lower level of plasma Aβ42/40 ratio than aPET negative subjects [31]. The correlation between low plasma Aβ42/40 ratio and aPET positivity is also seen in patients with SCD [26, 30] and in MCI patients [32, 35].

A single study found no significant difference in plasma Aβ42/40 ratio between aPET positive and negative patients [28].

Plasma Aβ as a cerebrospinal fluid Aβ surrogate

Plasma Aβ42 and Aβ40

In a study by Hanon et al. comparing subjects diagnosed with MCI and AD, a significant association was found between plasma and CSF levels of Aβ42 in both MCI patients and AD patients [36]. A positive association (r = 0.18, p < 0.001) was also found between plasma Aβ42 and CSF Aβ42 in SCD patients in a study by Verberk et al. They did not find a statistically significant association between plasma Aβ40 and CSF Aβ40 in the same study [26]. Feinkohl et al. found a significant but small association in AD patients and controls combined between plasma Aβ42 and CSF Aβ42 but an insignificant association with regards to Aβ40 [37]. In a study by Palmqvist et al. of cognitively unimpaired subjects with MCI and AD, both plasma Aβ42 and plasma Aβ40 were shown to be directly associated with CSF Aβ42/40 ratio [38].

In contrast, no significant correlation was found between either plasma Aβ42 or plasma Aβ40 and CSF levels in a combined study of patients with AD and demented controls without AD pathology [28].

Plasma Aβ42/40 ratio

Five studies reported correlations between Aβ42/40 ratio in plasma and CSF [28, 31, 35, 37, 38], and the results of the meta-analysis are shown in Figure 3. The random-effects model estimate is r = 0.50 (95% CI: 0.30-0.69) with an  of 79%. Heterogeneity is high, but the largest study by Palmqvist et al. is more than five times larger than the second-largest study, and the smaller studies are more different from each other (Feinkohl et al. and Schindler et al.) or exhibit low precision (Vogelgsang et al. and Pérez-Grijalba et al.) so we may assign a higher confidence to the study by Palmqvist et al.; but considering only the Palmqvist et al. study, estimate r = 0.52 (95% CI: 0.45-0.59) is not significantly different from the meta-analytical estimate.

A positive correlation between plasma Aβ42/40 ratio and CSF Aβ42/40 ratio was seen in cognitively normal subjects [31] (r = 0.66 (95% CI: 0.56-0.75)) and in a group comprising AD patients and demented patients without AD pathology (r = 0.425, p = 0.014) [28].

Feinkohl et al. found positive associations between plasma Aβ42/40 ratio and CSF Aβ42/40 ratio, Aβ42 and Aβ40 in subjects with AD and in cognitively normal subjects [37]. The association between plasma Aβ42/40 ratio and CSF Aβ42 was also found in SCD subjects r = 0.38, p < 0.001 [26]. In the study by Pérez-Grijalba et al. of cognitively normal subjects and patients with probable MCI, it was also shown that plasma Aβ42/40 ratio is positively correlated to CSF Aβ42 levels (r = 0.549, p < 0.001) and negatively correlated to CSF tau levels (tTau r = –0.314, p = 0.031; pTau r = –0.329, p = 0.040) [35].

Plasma Aβ as a biomarker in Alzheimer’s disease

Many studies investigating whether clinical AD and aPET positivity may be predicted by plasma Aβ have used different methodologies and analyses. The study of patients with MCI by Pérez-Grijalba et al. showed that during a follow-up time of two years, 52.4% of the MCI patients with a low plasma Aβ42/40 ratio (baseline below the median of the cohort) progressed to AD compared with 28.8% of the MCI patients with a high plasma Aβ42/40 ratio (baseline above the median of the cohort) [35]. The level of plasma Aβ42/40 ratio of the progressors was significantly lower than the level of non-progressors. This low plasma Aβ42/40 ratio level resulted in an approx. 70% increased risk among MCI patients of progressing to AD (hazard ratio (HR) = 1.687 (95% CI: 1.058-2.691), p = 0.028). Plasma Aβ42/40 ratio for discrimination between MCI progressors or non-progressors had a sensitivity and specificity above 70%, and a receiver-operating characteristic curve for the sensitivity/specificity trade-off had an area under the curve (AUC) of 0.857 [35].

Verberk et al. found an increased risk that SCD patients progressed clinically to MCI or AD if they had low levels of plasma Aβ42/40 ratio (HR = 2.31 (95% CI: 1.55-3.43)) or Aβ42 (HR = 1.74 (95% CI: 1.19-2.56)). Isolated plasma Aβ40 levels did not predict higher risk of progression from SCD to MCI or AD [26]. During a follow-up period, Schindler et al. found that cognitively normal patients who converted from aPET negative to aPET positive had lower baseline levels of plasma Aβ42/40 ratio (0.117 ± 0.008) than non-converters (0.128 ± 0.009), p < 0.01. A logistic regression model showed that aPET negative subjects with a low plasma Aβ42/40 ratio had a 15 times increased risk of converting to aPET positivity than subjects with a high plasma Aβ42/40 ratio [31].

Several studies have investigated models combining plasma Aβ42/40 ratio and other covariates. In cognitively normal subjects (including SMC subjects), a model combining age, APOE ɛ4 allele and plasma Aβ42/40 ratio predicted current aPET positivity with an AUC of 0.776 [29]. Furthermore, an AUC of 0.855 was found (in a cohort of patients with AD, MCI, young and old controls, n = 510) by Jang et al. combining the same covariates. Interestingly, AUC rose to 0.916 when further adding the cognitive stage as a covariate [32]. Pérez-Grijalba et al. found AUCs of 0.957 and 0.814 in controls and MCI patients, respectively, when investigating the ability of unadjusted plasma Aβ42/40 ratio to predict aPET positivity. In the study by Feinkohl et al. comprising AD patients and controls, plasma Aβ42/40 ratio, Aβ42 and Aβ40 discriminated poorly between AD and controls with AUC values ≤ 0.58 [37].


Plasma Aβ as a future biomarker

Currently, the clinical diagnosis of probable AD relies on a combination of clinical examination and neuropsychological test batteries standardised by a revised version of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) Alzheimer’s criteria [11]. However, even experienced clinicians will occasionally reach incorrect diagnoses. Hence, a study by Li et al. found that 22.64% of the study subjects who were diagnosed with probable AD according to the NINCDS-ADRDA Alzheimer’s criteria were aPET negative [11].

Different methods of measurement, diverse study populations and an incomplete knowledge of Aβ kinetics may complicate the united research on the subject. However, some patterns have been consistently demonstrated:

Plasma Aβ40: With the exception of an association between high MPP-treated plasma Aβ40 levels and aPET positivity in the study by Park et al. [27], the studies included in this systematic review all found no significant association of plasma Aβ40 with either aPET [26, 28-30] or CSF Aβ40 [26, 28, 37].

Plasma Aβ42: This biomarker has been suggested as the first detectable biomarker in plasma [24]. Some studies included in the present work have suggested an association between low plasma Aβ42 and low CSF Aβ42 [26, 36] or aPET positivity [26]. Other studies reported no association between plasma Aβ42 and aPET [28-30] or CSF Aβ42 [28].

Plasma Aβ42/40 ratio: The majority of results extracted from the included articles of this systematic review reported of an inverse association between plasma Aβ42/40 ratio and aPET positivity [11, 26, 27, 29, 30-35]. Only one of the included articles reported no association between plasma Aβ42/40 ratio and aPET positivity [28].

A direct association between plasma Aβ42/40 ratio and CSF Aβ42/40 ratio has been noted in some studies [28, 31]. However, other studies show a direct association between plasma Aβ42/40 ratio and CSF Aβ42 [26, 35, 37]. Plasma Aβ42/40 ratio has further been inversely associated with CSF tau levels. The high CSF tau levels combined with low CSF Aβ42 together constitute a typical AD profile [35].

Methods of measurement

The laboratory handling of measurements of plasma Aβ partly explains the observed variation in concentrations and ratios since detected differences in plasma Aβ are very small and not all processes have been automated [33]. The great variation in assays and technical methods of measuring plasma Aβ may hinder consistent validation of its potential as a plasma biomarker.

Study populations

The study populations in the included studies have comprised the entire spectrum of the AD continuum from cognitively normal controls to dementia. Plasma Aβ levels vary between cognitive stages, leading to different between-study concentrations and ratios. To validate the concept of plasma Aβ as an early biomarker predicting progression to AD, longitudinal studies of cognitively normal elderly people are warranted.

Aβ kinetics

It seems evident that Aβ originates from brain tissue. However, some portion of Aβ is also thought to originate from peripheral tissue [39]. In plasma, Aβ is met by several components such as protein-binding albumin, proteases, phosphatases, etc. [27]. These plasma components may very well be responsible for some of the conflicting results on plasma Aβ reported by different studies.

Summary, limitations and strengths

The forest plots on Figure 2 and Figure 3 illustrate the overall strength of the correlation between plasma Aβ42/40 ratio and aPET positivity (r = –0.48 (95% CI: –0.65-–0.31)), and plasma Aβ42/40 ratio and CSF Aβ42/40 ratio (r = 0.50 (95% CI: 0.30-0.69)).

The studies included in the meta-analysis exhibited substantial heterogeneity, which limits the generalisability of the results and lowers the confidence in the meta-analytic model estimates. This may be due to the considerable variance in studies partly produced by the many different included subjects; cognitively unimpaired, MCI, AD patients, etc. However, the forest plots provide a visual summary of the individual studies and from a statistical point of view we can assign higher confidence in the more strongly powered and more precise studies and lower confidence in the smaller studies. The direction of the effects is consistent; plasma Aβ42/40 ratio is positively correlated with CSF Aβ42/40 ratio and negatively correlated with aPET.

None the less, even though the association between amyloid pathology and plasma Aβ42/40 ratio is generally solid, the robustness of Aβ42/40 ratio as a marker for AD pathology may be questioned due to the small fold changes between amyloid positivity versus negativity. Also, it should be mentioned that emerging methods for biomarker detection such as mass spectrometry have shown a potentially better performance than conventional immunoassays [40, 41], and several other biomarkers and biomarker combinations warrant further investigation. For instance, Janelidze et al. found that a combination of plasma Aβ42/40 ratio and plasma phosphorylated-tau217 in cognitively unimpaired subjects resulted in an AUC in the 0.83-0.86 range [42].

This systematic review has some weaknesses. The different study designs of the included studies prevent direct comparisons. The cognitive stages referred to in the studies are very similar. However, different definitions and cut-offs have been used. Measurements of plasma Aβ have been interchangeably referred to as plasma Aβ in this review even though some articles refer to the measures of total plasma Aβ (e.g., TP42/40 [35]). Lastly, the term aPET has been used interchangeably about PET assessing brain amyloidosis regardless of the cut-off values and type of tracer being used.

The greatest strength of this systematic review lies in the strict inclusion of studies in which subjects had been either examined by aPET or CSF biomarker analysis (or both).

The potential of a plasma biomarker

If a plasma biomarker of AD can be validated, it will probably reduce societal costs markedly as the need for aPET and CSF biomarker analyses will diminish, whereas the usage of these methods may be targeted where most relevant. It would potentially identify subjects with prodromal AD eligible for clinical trials, thus inducing a faster development of new treatments for AD. Lastly, it will enable general practitioners to identify patients at risk of developing AD much earlier than is currently the case, using a simple blood sample. Given the epidemiology of AD and calculated risk of double prevalence within the next decades [43, 44], the importance of a valid, early and cost-efficient biomarker is high.


Most studies have found no significant association between plasma Aβ40 and aPET or CSF Aβ40. The studies of plasma Aβ42 have yielded somewhat contradictory results with some studies indicating an association with aPET and CSF Aβ42 and other studies showing no association.

The predictive potential of plasma Aβ42/40 ratio seems more promising. Plasma Aβ42/40 ratio is positively correlated with CSF Aβ42/40 ratio at r = 0.50 and negatively correlated with aPET at r = –0.48. There was substantial between-study heterogeneity, but the overall direction of these effects remains consistent. Some of the heterogeneity stems from differences in study population, laboratory and assay parameters.

Some studies have longitudinal follow-up and investigated how low CSF or plasma Aβ42/40 ratio predicts conversion to AD and report AUCs up to 0.86. However, larger longitudinal studies are required to fully characterise the diagnostic utility of plasma Aβ.

Correspondence Svend Ubbe Ebbesen. E-mail:

Accepted 6 March 2023

Conflicts of interest Potential conflicts of interest have been declared. Disclosure forms provided by the authors are available with the article at

Cite this as Dan Med J 2023;70(6):A07220446


  1. Buchhave P, Minthon L, Zetterberg H et al. Cerebrospinal fluid levels of β-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia. Arch Gen Psychiatry. 2012;69(1):98-106.
  2. Jack CR Jr, Holtzman DM. Biomarker modeling of Alzheimer’s disease. Neuron. 2013;80(6):1347-58.
  3. Dubois B, Hampel H, Feldman HH et al. Preclinical Alzheimer’s disease: definition, natural history, and diagnostic criteria. Alzheimers Dement. 2016;12(3):292-323.
  4. Villemagne VL, Burnham S, Bourgeat P et al. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol. 2013;12(4):357-67.
  5. Jack CR Jr, Knopman DS, Jagust WJ et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12(2):207-16.
  6. Sperling R, Mormino E, Johnson K. The evolution of preclinical Alzheimer’s disease: implications for prevention trials. Neuron. 2014;84(3):608-22.
  7. Kang J, Lemaire HG, Unterbeck A et al. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature. 1987;325(6106):733-6.
  8. Masters CL, Bateman R, Blennow K et al. Alzheimer’s disease. Nat Rev Dis Primers. 2015;1:15056.
  9. Roberts KF, Elbert DL, Kasten TP et al. Amyloid-β efflux from the central nervous system into the plasma. Ann Neurol. 2014;76(6):837-44.
  10. Jack CR Jr, Bennett DA, Blennow K et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535-62.
  11. Li WW, Shen YY, Tian DY et al. Brain amyloid-β deposition and blood biomarkers in patients with clinically diagnosed Alzheimer’s disease. J Alzheimers Dis. 2019;69(1):169-78.
  12. Olsson B, Lautner R, Andreasson U et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15(7):673-84.
  13. Andreasen N, Hesse C, Davidsson P et al. Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. Arch Neurol. 1999;56(6):673-80.
  14. Tapiola T, Alafuzoff I, Herukka SK et al. Cerebrospinal fluid {beta}-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol. 2009;66(3):382-9.
  15. Fagan AM, Mintun MA, Mach RH et al. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol. 2006;59(3):512-9.
  16. Portelius E, Tran AJ, Andreasson U et al. Characterization of amyloid beta peptides in cerebrospinal fluid by an automated immunoprecipitation procedure followed by mass spectrometry. J Proteome Res. 2007;6(11):4433-9.
  17. Portelius E, Westman-Brinkmalm A, Zetterberg H et al. Determination of beta-amyloid peptide signatures in cerebrospinal fluid using immunoprecipitation-mass spectrometry. J Proteome Res. 2006;5(4):1010-6.
  18. Hansson O, Zetterberg H, Buchhave P et al. Prediction of Alzheimer’s disease using the CSF Abeta42/Abeta40 ratio in patients with mild cognitive impairment. Dement Geriatr Cogn Disord. 2007;23(5):316-20.
  19. Lewczuk P, Esselmann H, Otto M et al. Neurochemical diagnosis of Alzheimer’s dementia by CSF Abeta42, Abeta42/Abeta40 ratio and total tau. Neurobiol Aging. 2004;25(3):273-81.
  20. Wiltfang J, Esselmann H, Bibl M et al. Amyloid beta peptide ratio 42/40 but not A beta 42 correlates with phospho-Tau in patients with low- and high-CSF A beta 40 load. J Neurochem. 2007;101(4):1053-9.
  21. Lewczuk P, Lelental N, Spitzer P et al. Amyloid-β 42/40 cerebrospinal fluid concentration ratio in the diagnostics of Alzheimer’s disease: validation of two novel assays. J Alzheimers Dis. 2015;43(1):183-91.
  22. Page MJ, McKenzie JE, Bossuyt PM et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71.
  23. Welcome to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) website! (Mar 2023).
  24. Palmqvist S, Insel PS, Stomrud E et al. Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer’s disease. EMBO Mol Med. 2019;11(12):e11170.
  25. Jessen F, Amariglio RE, van Boxtel M et al. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer’s disease. Alzheimers Dement. 2014;10(6):844-52.
  26. Verberk IMW, Slot RE, Verfaillie SCJ et al. Plasma amyloid as prescreener for the earliest Alzheimer pathological changes. Ann Neurol. 2018;84(5):648-58.
  27. Park JC, Han SH, Cho HJ et al. Chemically treated plasma Aβ is a potential blood-based biomarker for screening cerebral amyloid deposition. Alzheimers Res Ther. 2017;9(1):20.
  28. Vogelgsang J, Shahpasand-Kroner H, Vogelgsang R et al. Multiplex immunoassay measurement of amyloid-β(42) to amyloid-β(40) ratio in plasma discriminates between dementia due to Alzheimer’s disease and dementia not due to Alzheimer’s disease. Exp brain Res. 2018;236(5):1241-50.
  29. Chatterjee P, Elmi M, Goozee K et al. Ultrasensitive detection of plasma amyloid-β as a biomarker for cognitively normal elderly individuals at risk of Alzheimer’s disease. J Alzheimers Dis. 2019;71(3):775-83.
  30. de Rojas I, Romero J, Rodríguez-Gomez O et al. Correlations between plasma and PET beta-amyloid levels in individuals with subjective cognitive decline: the Fundació ACE Healthy Brain Initiative (FACEHBI). Alzheimers Res Ther. 2018;10(1):119.
  31. Schindler SE, Bollinger JG, Ovod V et al. High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019;93(17):e1647-e1659.
  32. Jang H, Kim JS, Lee HJ et al. Performance of the plasma Aβ42/Aβ40 ratio, measured with a novel HPLC-MS/MS method, as a biomarker of amyloid PET status in a DPUK-KOREAN cohort. Alzheimers Res Ther. 2021;13(1):179.
  33. Doecke JD, Pérez-Grijalba V, Fandos N et al. Total Aβ(42)/Aβ(40) ratio in plasma predicts amyloid-PET status, independent of clinical AD diagnosis. Neurology. 2020;94(15):e1580-e1591.
  34. Pérez-Grijalba V, Arbizu J, Romero J et al. Plasma Aβ42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 study. Alzheimers Res Ther. 2019;11(1):96.
  35. Pérez-Grijalba V, Romero J, Pesini P et al. Plasma Aβ42/40 ratio detects early stages of Alzheimer’s disease and correlates with CSF and neuroimaging biomarkers in the AB255 study. J Prev Alzheimer’s Dis. 2019;6(1):34-41.
  36. Hanon O, Vidal JS, Lehmann S et al. Plasma amyloid levels within the Alzheimer’s process and correlations with central biomarkers. Alzheimers Dement. 2018;14(7):858-68.
  37. Feinkohl I, Schipke CG, Kruppa J et al. Plasma amyloid concentration in Alzheimer’s disease: performance of a high-throughput amyloid assay in distinguishing Alzheimer’s disease cases from controls. J Alzheimers Dis. 2020;74(4):1285-94.
  38. Palmqvist S, Janelidze S, Stomrud E et al. Performance of fully automated plasma assays as screening tests for Alzheimer disease-related β-amyloid status. JAMA Neurol. 2019;76(9):1060-9.
  39. Blennow K, Zetterberg H. Biomarkers for Alzheimer’s disease: current status and prospects for the future. J Intern Med. 2018;284(6):643-63.
  40. Nakamura A, Kaneko N, Villemagne VL et al. High performance plasma amyloid-β biomarkers for Alzheimer’s disease. Nature. 2018;554(7691):249-54.
  41. Ovod V, Ramsey KN, Mawuenyega KG et al. Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement. 2017;13(8):841-9.
  42. Janelidze S, Palmqvist S, Leuzy A et al. Detecting amyloid positivity in early Alzheimer’s disease using combinations of plasma Aβ42/Aβ40 and p-tau. Alzheimers Dement. 2022;18(2):283-293.
  43. World Alzheimer Report 2015. Alzheimer’s Disease International, 2015. (Mar 2023).
  44. Dementia in Europe Yearbook 2019. Alzheimer Europe, 2019. (Mar 2023).