Correction to: Cerebrospinal fluid amyloid-ß 2-42 is decreased in Alzheimer's, but not in frontotemporal dementia.

The respective first and last authors of this article, Mirko Bibl and Jens Wiltfang, would like to clarify the issue of the seeming duplicate publication of a figure in two articles.

Neurochemical biomarkers in Alzheimer's disease and related disorders.

Neurochemical biomarkers for diagnosing dementias are currently under intensive investigation and the field is rapidly expanding. The main protagonists and the best defined among them are cerebrospinal fluid levels of Aß42, tau and its phosphorylated forms (p-tau). In addition, novel cerebrospinal fluid biomarkers are emerging and their multiparametric assessment seems most promising for increasing the accuracy in neurochemical dementia diagnostics. The combined assessment of Aß42 and p-tau has recently shown value for diagnosing prodromal states of Alzheimer's dementia, that is, mild cognitive impairment. Disease-specific biomarkers for other degenerative dementias are still missing, but some progress has recently been made. As lumbar puncture is an additional burden for the patient, blood-based neurochemical biomarkers are definitely warranted and promising new discoveries have been made in this direction. These diagnostic developments have implicit therapeutic consequences and give rise to new requirements for future neurochemical dementia diagnostics.

Plasma amyloid-beta peptides in acute cerebral ischemia: a pilot study.

BACKGROUND: Blood-based tests for a rapid and valid diagnosis as well as outcome prognosis of acute stroke are desirable. Recently, plasma Aß40 was suggested as an independent cerebrovascular risk factor candidate. METHODS: We investigated eight plasma samples of patients with clinical signs of acute cerebral ischemia for derangements of plasma amyloid-beta (Aß) peptide patterns as compared to 13 patients with other neuropsychiatric diseases. For the analysis of plasma, we used immunoprecipitation followed by the quantitative Aß-SDS-PAGE/immunoblot. RESULTS: The major outcome was a striking decrease of Aß1-40 in plasma paralleled by an increase in the ratio of Aß1-38/Aß1-40 in two patients with acute stroke. Interestingly, these patients had an onset of symptoms within only 2-4 hr before venous puncture and there was a strong correlation of Aß1-38/Aß1-40 levels with the time span between onset of symptoms and venous puncture. CONCLUSION: From these results, we suggest the ratio of plasma Aß1-38/Aß1-40 as a possible biomarker for the early diagnosis of acute stroke.

Characterization of cerebrospinal fluid aminoterminally truncated and oxidized amyloid-ß peptides.

PURPOSE: Carboxyterminally elongated and aminoterminally truncated Aß peptides as well as their pyroglutamate and oxidized derivates are major constituents of human amyloid plaques. The objective of the present study was to characterize aminoterminally truncated or oxidized Aß38, Aß40, and Aß42 peptide species in immunoprecipitated human cerebrospinal fluid (CSF). EXPERIMENTAL DESIGN: We invented a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol and used the Aß-SDS-PAGE/immunoblot for subsequent analysis of CSF Aß peptide patterns. RESULTS: In the present study, we identified the aminoterminally truncated Aß peptides 2-40 and 2-42 as well as oxidized forms of Aß1-38 and Aß1-42 in CSF. Our protocol allowed the quantification of a pattern of Aß peptides 1-38(ox), 2-40, and 2-42 in addition to the well known panel of Aß 1-37, 1-38, 1-39, 1-40, 1-40(ox), and 1-42 in a group of seven patients with peripheral polyneuropathy. CONCLUSIONS AND CLINICAL RELEVANCE: In the present approach, we could broaden the range of quantifiable Aß peptides described in previous studies (i.e., 1-37, 1-38, 1-39, 1-40, 1-40(ox), and 1-42) by Aß 1-38(ox), 2-40, and 2-42. An exact analysis of CSF Aß peptides regarding their carboxy- and aminoterminus as well as posttranslational modification seems promising with respect to diagnostic and pathogenic aspects.

Cerebrospinal fluid amyloid-ß 2-42 is decreased in Alzheimer's, but not in frontotemporal dementia.

Alzheimer's dementia (AD) and frontotemporal dementias (FTD) are common and their clinical differential diagnosis may be complicated by overlapping symptoms, which is why biomarkers may have an important role to play. Cerebrospinal fluids (CSF) Aß2-42 and 1-42 have been shown to be similarly decreased in AD, but 1-42 did not display sufficient specificity for exclusion of other dementias from AD. The objective of the present study was to clarify the diagnostic value of Aß2-42 peptides for the differential diagnosis of AD from FTD. For this purpose, 20 non-demented disease controls (NDC), 22 patients with AD and 17 with FTD were comparatively analysed by a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol with subsequent Aß-SDS-PAGE/immunoblot, allowing the quantification of peptides 1-38(ox), 2-40 and 2-42 along with Aß 1-37, 1-38, 1-39, 1-40, 1-40(ox) and 1-42. CSF Aß1-42 was decreased in AD as compared to NDC, but not to FTD. In a subgroup of the patients analyzed, the decrease of Abeta2-42 in AD was evident as compared to both NDC and FTD. Aß1-38 was decreased in FTD as compared to NDC and AD. For differentiating AD from FTD, Aß1-42 demonstrated sufficient diagnostic accuracies only when combined with Aß1-38. Aß2-42 yielded diagnostic accuracies of over 85 % as a single marker. These accuracy figures could be improved by combining Aß2-42 to Aß1-38. Aß2-42 seems to be a promising biomarker for differentiating AD from other degenerative dementias, such as FTD.

Aminoterminally truncated and oxidized amyloid-ß peptides in the cerebrospinal fluid of Alzheimer's disease patients.

Carboxyterminally elongated and aminoterminally truncated amyloid-ß (Aß) peptides and their oxidized derivates are major constituents of human amyloid plaques. The objective of the present study was to clarify the diagnostic impact of the Aß peptides 1-38ox, 2-40, and 2-42 peptides on the neurochemical cerebrospinal fluid (CSF) diagnosis of Alzheimer's disease (AD). For this purpose, 22 patients with AD and 20 non-demented disease controls (NDC) were comparatively analyzed for their cerebrospinal fluid pattern of Aß1-38ox, Aß2-40, and Aß2-42 along with Aß1-37, Aß1-38, Aß1-39, Aß1-40, Aß1-40ox, and Aß1-42 using a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol and subsequent analysis in the Aß-SDS-PAGE/immunoblot. The Aß peptides 1-38ox, 2-40, and 2-42 could not be consistently detected in the investigated CSF samples, which applied to samples from AD and NDC patients alike. Otherwise, our approach revealed a striking decrease of Aß1-42 and Aß2-42, but not of Aß1-38ox and Aß2-40 in AD. Both Aß1-42 and Aß2-42 reached reasonable accuracies for diagnosing AD alone as well as in relation to Aß1-40, Aß1-38, or the sum of all measured Aß peptides. Aß1-38ox was negatively correlated to the Mini-Mental Status Examination score of AD patients, indicating that this peptide to linked to disease severity. We conclude that an exact analysis of CSF Aß peptides regarding their carboxy- and aminoterminus as well as posttranslational modification may be a promising approach for diagnosing and tracking AD.

Stability of amyloid-ß peptides in plasma and serum.

Plasma amyloid-ß peptide (Aß) levels have been suggested as a biomarker candidate for detecting incipient AD. Aß peptides are known to be sensitive to distinct preanalytical sample handling, which calls for standardised preanalytical procedures. We investigated serum and plasma samples of 19 patients with no clinical signs of dementia for different preanalytical sample handlings. Both serum and plasma were analysed by the one-dimensional Aß-SDS-PAGE/immunoblot, either immediately or after storage at room temperature for 24 and 48 h, respectively. The panel of Aß1-37/38/39/40/42 and Aß2-40 was evaluated. In both analytical matrices, sample storage led to a significant loss of measurable peptide levels. This effect was most pronounced during the first 24 h of storage and stronger in serum than in plasma. There were no significant differences between the distinct analysed Aß peptide species regarding these results. The ratios of peptides (e.g. Aß1-42/Aß1-40 and Aß1-42/Aß1-38) displayed a higher stability under the influence of storage than each single peptide. In conclusion, plasma may be more appropriate than serum for analysing Aß peptides for routine application. At least, the analysis should be done within 24 h and peptide ratios should be created to minimise artificial results.

Standardization of preanalytical aspects of cerebrospinal fluid biomarker testing for Alzheimer's disease diagnosis: a consensus paper from the Alzheimer's Biomarkers Standardization Initiative.

BACKGROUND: Numerous studies show that the cerebrospinal fluid biomarkers total tau (T-tau), tau phosphorylated at threonine 181 (P-tau(181P)), and amyloid-ß (1-42) (Aß(1-42)) have high diagnostic accuracy for Alzheimer's disease. Variability in concentrations for Aß(1-42), T-tau, and P-tau(181P) drives the need for standardization. METHODS: Key issues were identified and discussed before the first meeting of the members of the Alzheimer's Biomarkers Standardization Initiative (ABSI). Subsequent ABSI consensus meetings focused on preanalytical issues. RESULTS: Consensus was reached on preanalytical issues such as the effects of fasting, different tube types, centrifugation, time and temperature before storage, storage temperature, repeated freeze/thaw cycles, and length of storage on concentrations of Aß(1-42), T-tau, and P-tau(181P) in cerebrospinal fluid. CONCLUSIONS: The consensus reached on preanalytical issues and the recommendations put forward during the ABSI consensus meetings are presented in this paper.

CSF amyloid-ß peptides in neuropathologically diagnosed dementia with Lewy bodies and Alzheimer's disease.

Appropriate treatment of dementia requires biomarkers that provide an exact and differential diagnosis. We recently presented differentially expressed amyloid-ß (Aß) peptide patterns in cerebrospinal fluid (CSF) as biomarker candidates for neurochemical diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). The objective of the present study was to investigate CSF Aß peptide patterns in both neuropathologically and clinically defined diagnostic groups of AD and DLB. Using the quantitative Aß-SDS-PAGE/immunoblot, we analyzed CSF samples of neuropathologically defined patients with AD (definite AD, dAD; n = 11) and DLB (definite, dDLB; n = 12). We compared absolute and relative quantities of CSF Aß-peptides with a larger cohort of clinically diagnosed patients with probable AD (pAD; n = 71), probable DLB (pDLB; n = 32), and non-demented controls (NDC; n = 71). Each neuropathologically and clinically defined diagnostic group showed a similar relative distribution of CSF Aß-peptides (Aß(1-X%)). Aß(1-42%) was lowered in dAD compared to NDC (p = 1.6 × 10⁻7, but did not differ between dAD and pAD. Aß(1-40ox%) was elevated in dDLB as compared to NDC (p = 1.8 × 10⁻5, but did not differ between dDLB and pDLB. Thus, we were able to confirm previous results on Aß peptide patterns in neuropathologically characterized patients with AD and DLB. Our results underline the usefulness of the CSF Aß(1-42%) and Aß(1-40ox%) as diagnostic biomarkers for AD and DLB, respectively.

Different CSF ß-amyloid processing in Alzheimer's and Creutzfeldt-Jakob disease.

Decreased levels of ß-amyloid (Aß) 1-42 in cerebrospinal fluid (CSF) are characteristic for Alzheimer's disease (AD) and are also evident in Creutzfeldt-Jakob disease (CJD). Aß plaques are thought to be responsible for this decrease in AD patients, whereas such Aß plaques are rarely seen in CJD. To investigate the Aß pattern in brain and CSF of neuropathologically confirmed CJD and AD patients we used an electrophoretic method to investigate Aß peptide fractions which are not accessible to ELISA and immunohistochemistry. We analyzed Aß peptides in the CSF of autopsy-confirmed CJD and AD patients and the corresponding brain homogenates using a quantitative urea-based Aß electrophoresis immunoblot (Aß-SDS-PAGE/immunoblot).The CSF Aß1-42 decrease correlated with the brain Aß load in AD, but not in CJD. There was no difference in the soluble fractions of brain homogenate in AD and CJD. We therefore conclude that different mechanisms in AD and CJD are responsible for the Aß1-42 decrease in the CSF.

Cerebrospinal fluid tau, p-tau 181 and amyloid-ß38/40/42 in frontotemporal dementias and primary progressive aphasias.

BACKGROUND/AIMS: We determined cerebrospinal fluid (CSF) concentrations of amyloid-ß (Aß)(1-38), Aß(1-40), Aß(1-42), total tau and phospho-tau (p-tau) in order to study their differential expression in frontotemporal dementia (FTD, n = 25) and primary progressive aphasia (PPA, n = 12) as compared to Alzheimer's dementia (AD, n = 25) and nondemented controls (n = 20). METHODS: Commercially available ELISA and electrochemiluminescence methods were applied. RESULTS: High CSF p-tau and low ratios of Aß(1-42)/Aß(1-40) and Aß(1-42)/Aß(1-38), respectively, were specific for AD. CSF Aß(1-38) was reduced in FTD as compared to each of the other diagnostic groups, including PPA. CSF tau and p-tau levels were elevated in PPA as compared to FTD. CONCLUSION: This is the first detailed report on biomarker patterns in PPA, indicating distinct CSF biomarker patterns in FTD and PPA as major subgroups of frontotemporal lobar degeneration. The diagnostic and pathophysiological implications of our results warrant further studies on larger and neuropathologically diagnosed patient populations.

Combined Analysis of CSF Tau, Aß42, Aß1-42% and Aß1-40% in Alzheimer's Disease, Dementia with Lewy Bodies and Parkinson's Disease Dementia.

We studied the diagnostic value of CSF Aß42/tau versus low Aß1-42% and high Aß1-40(ox)% levels for differential diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), respectively. CSF of 45 patients with AD, 15 with DLB, 21 with Parkinson's disease dementia (PDD), and 40 nondemented disease controls (NDC) was analyzed by Aß-SDS-PAGE/immunoblot and ELISAs (Aß42 and tau). Aß42/tau lacked specificity in discriminating AD from DLB and PDD. Best discriminating biomarkers were Aß1-42% and Aß1-40(ox)% for AD and DLB, respectively. AD and DLB could be differentiated by both Aß1-42% and Aß1-40(ox)% with an accuracy of 80% at minimum. Thus, we consider Aß1-42% and Aß1-40(ox)% to be useful biomarkers for AD and DLB, respectively. We propose further studies on the integration of Aß1-42% and Aß1-40(ox)% into conventional assay formats. Moreover, future studies should investigate the combination of Aß1-40(ox)% and CSF alpha-synuclein for the diagnosis of DLB.

Quantification of amyloid-beta 40 in cerebrospinal fluid.

BACKGROUND: Truncated forms and full-length forms of the amyloid-beta 40 (Abeta40) are key molecules in the pathogenesis of dementia, and are detectable in CSF. Reliable methods to detect these biomarkers in CSF are of great importance for understanding the disease mechanisms and for diagnostic purposes. METHODS: VU-alpha-Abeta40, a monoclonal antibody (mAb) specifically detecting Abeta40, was generated and characterized by solid and fluid phase ELISA, surface plasmon resonance spectroscopy (SPRS), immunoprecipitation (IP), immunohistochemical and Western blot (WB) analysis. In addition, an ELISA with VU-alpha-Abeta40 as catching and 6E10 as detecting mAbs was set up and validated. This ELISA was used to measure Abeta40 in CSF of controls (N=27), patients with Alzheimer's disease (AD; N=20), frontotemporal lobe dementia (FTLD; N=14), noninflammatory (N=15) and inflammatory (N=15) neurological conditions. RESULTS: VU-alpha-Abeta40 specifically recognizes Abeta40 with high affinity (K(A)=1.3x10(9) M(-1)) and detects Abeta40 in AD brain specimens. The developed sandwich ELISA has a detection limit of 0.21 ng/mL, a mean recovery of 90%, and an intra- and inter-assay CV of 1.4% and 7.3%. FTLD patients had a lower mean level of Abeta40 (8.8 (1.9) ng/mL) than controls (12.0 (1.7) ng/mL); p<0.01). CONCLUSIONS: VU-alpha-Abeta40 was successfully implemented in an ELISA which enables us to measure Abeta40 accurately in human CSF. Clinical validation revealed lower levels of Abeta40 in FTLD patients. This finding opens new possibilities for early and differential diagnosis of dementia.

Measurement of ERK 1/2 in CSF from patients with neuropsychiatric disorders and evidence for the presence of the activated form.

The clinical diagnosis of neurodegenerative disorders can be supported by soluble biomarkers in cerebrospinal fluid (CSF), such as tau protein, phospho-tau, and amyloid-beta peptides. In particular, increased CSF levels of phospho-tau in Alzheimer's disease appear to reflect disease specific pathological processes. We report here evidence for the presence of soluble MAP-kinase ERK1/2 in a small set of human CSF samples from patients with Alzheimer's disease, frontotemporal degeneration, and mild cognitive impairment. The level of total ERK1/2 in CSF as measured by electrochemiluminescent assay was correlated with that of total tau and phospho-tau. A small fraction of ERK1/2 in a pooled CSF sample was found to be in the doubly phosphorylated (activated) state. Our findings suggest that i) MAP kinase ERK1/2 is apparently released under neurodegenerative conditions in parallel with tau and phospho-tau and ii) in the future, it might be possible to find in CSF samples evidence for disease related alterations in brain kinase signaling pathways by use of highly sensitive and activation-state specific anti-kinase antibodies.

Combined CSF tau, p-tau181 and amyloid-beta 38/40/42 for diagnosing Alzheimer's disease.

Cerebrospinal fluid (CSF) concentrations of amyloid-beta (Abeta) 1-38, 1-40, 1-42, total-tau and phospho-tau in samples from 156 patients with Alzheimer's disease (AD) (n = 44), depressive cognitive complainers (DCC, n = 25) and various other forms of non-Alzheimer dementias (NAD, n = 87) were analyzed by electrochemiluminescence and enzyme linked immunosorbent assay, respectively. A significant decrease of CSF Abeta1-42 was the most powerful single marker for differentiation of AD from DCC, yielding accuracies of beyond 85%. Increased p-tau and the ratio Abeta1-42/Abeta1-38 yielded accuracies of beyond 80 and 85%, respectively, to discriminate AD versus NAD. Combining p-tau with Abeta1-42/Abeta1-38 resulted in a sensitivity of 94% for detection of AD and 85% specificity for excluding NAD. Decreased CSF Abeta1-42 represents a core biomarker for AD. The lack of specificity for exclusion of NAD can be most effectively compensated by the ratio Abeta1-42/Abeta1-38. The ratio Abeta1-42/Abeta1-38/p-tau powerfully discriminates AD versus NAD and fulfils the accuracy requirements for an applicable screening and differential diagnostic AD biomarker.

Adherence-dependent shifts in the patterns of beta-amyloid peptides secreted by human mononuclear phagocytes.

Cells of the mononuclear phagocyte system are closely associated with vascular and neuritic beta-amyloid deposits in Alzheimer's disease. Using one-dimensional and newly developed two-dimensional Abeta-SDS-PAGE Western immunoblot techniques (1D/2D-Abeta-WIB) we investigated the patterns of Abeta peptides released by primary non-adherent and adherence-activated human mononuclear phagocytes in vitro. An overall increase of total released Abeta peptides (Abeta(total)) was observed in adherence-activated mononuclear phagocyte cultures. 2D-Abeta-WIB revealed that the proportion of Abeta(1-40) decreased significantly to 50.2+/-5.4% (n=10) of Abeta(total) compared to 65.9+/-5.6% (n=7) in non-adherent cultures (p<0.0001, t=5.82). Abeta(1-42) accounted for only 3.0+/-2.1% of Abeta(total) and its proportion did not change significantly upon adherence (2.8+/-0.5% of Abeta(total)). In adherence-activated cultures we detected pronounced shifts in the fractional pattern of released Abeta peptides in favour of N-truncated species. The second most prominent Abeta peptide accounted for as much as 12.7+/-3.0% of Abeta(total) (2.0+/-1.2% in non-adherent cultures; p<0.0001, t=9.00) and was identified as Abeta(2-40) by comigration with a synthetic peptide and by N-terminal-specific antibodies. A strong increase of a further Abeta immunoreactive spot migrating at pI 5.45 was observed. It accounted for 9.2+/-1.7% of Abeta(total) as compared to 1.0+/-0.9% in non-adherent cultures (p<0.0001, t=11.61) and presumably represented a variant of Abeta(2-40) as determined by C-terminal Abeta(40)-specific immunoprecipitation and N-terminal-specific immunodetection. Thus, mononuclear phagocytes might be one source of the N-truncated Abeta peptides regularly found in human plasma and are less likely to contribute substantially to plasma Abeta(1-42).

Cerebrospinal fluid neurochemical phenotypes in vascular dementias: original data and mini-review.

BACKGROUND/AIMS: The study evaluated the patterns of cerebrospinal fluid (CSF), amyloid-beta (Abeta) peptides, total tau and phospho-tau among Alzheimer's disease (AD) and vascular dementias (VAD). METHODS: Abeta-SDS-PAGE immunoblot and commercially available ELISAs were applied to the CSF analysis of 52 patients with probable (n = 21) and possible (n = 16) VAD, AD with cerebrovascular disease (n = 15), 30 patients with probable AD and 30 nondemented disease controls. RESULTS: AD and AD with cerebrovascular disease displayed a similar neurochemical phenotype in contrast to nondemented disease controls and probable VAD with regard to tau, p-tau, Abeta1-40(ox) and Abeta1-42%. Possible VAD displayed AD-like changes only for Abeta1-40(ox) and Abeta1-42%. CONCLUSION: CSF neurochemical phenotypes sufficiently discriminate probable AD and VAD from each other, but their diagnostic value is limited in case of no clear-cut clinical appearance, such as possible VAD. Conversely, CSF Abeta peptides and p-tau levels may help estimate the involvement of AD-like pathophysiological pathways in VAD subgroups.

Multiplexed quantification of dementia biomarkers in the CSF of patients with early dementias and MCI: a multicenter study.

In this report we evaluated the clinical performance of APOE genotyping and three protein biomarkers (total tau, beta-amyloid(1-42), and tau phosphorylated at threonine 181) in a prospective multicenter study using the INNO-BIA AlzBio3 assay applied on Luminex platform. Concentration of biomarkers of Alzheimer's disease in cerebrospinal fluid (CSF) was measured with multiplexing technology (n=223), and compared to the results of ELISA assays in patients with early dementias or mild cognitive impairment (MCI) collected at 12 gerontopsychiatric university departments, and APOE genotyping was performed. Concentrations of Abeta(1-42) were statistically significantly lower in MCI-AD subjects compared to MCI-O, and significantly lower in D-AD patients compared to MCI-O. P-tau(181P) concentrations were significantly higher in MCI-AD patients compared to MCI-O, and significantly higher in D-AD patients compared to MCI-O. The total tau concentrations in MCI-AD patients were significantly higher compared to MCI-O, and higher in D-AD compared to MCI-O, moreover, the concentration of total tau was significantly higher in D-AD compared to MCI-AD patients. For the differential diagnosis between D-AD and D-O, the optimal cutoff concentration of Abeta(1-42) was 197.7 pg/mL, and that for P-tau(181P) was 47.9 pg/mL. These cutoff values were also applied to discriminate between MCI-AD and MCI-O subjects. Simultaneous measurement of the biomarkers significantly improves management of the samples and quality control of the assays' performance.

CSF amyloid-ß 1-38 and 1-42 in FTD and AD: Biomarker performance critically depends on the detergent accessible fraction.

Cerebrospinal fluid (CSF) Aß1-38, Aß1-40, and Aß1-42 were comparatively analyzed by amyloid-beta SDS-PAGE with Western immunoblot (Aß-SDS-PAGE/immunoblot), electrochemiluminescence detection and ELISA (MSD/ELISA) in patients with Alzheimer's disease (AD, n = 40), frontotemporal dementia (FTD, n = 30), and other dementias (n = 50) and nondemented disease controls (n = 30). CSF Aß-peptide concentrations were higher and selective decreases of CSF Aß1-38 in FTD and Aß1-42 in AD were more evident as measured after SDS-denaturizing of samples by Aß-SDS-PAGE/immunoblot. The SDS-accessible pool of CSF Aß1-38 and Aß1-42, represented by the individual gain of Aß-peptide yield using Aß-SDS-PAGE/immunoblot, was reduced in both FTD and AD. Accordingly, biomarker accuracies of Aß1-38 and Aß1-42 for detection of FTD and AD, respectively declined as determined by MSD/ELISA. We conclude that a pool of CSF Aß1-38 and Aß1-42, which shows disease-specific reductions in FTD and AD, may be bound to carriers and can be released by SDS. Assessing this SDS-accessible Aß-peptide pool may crucially enhance the accuracy of CSF biomarker tests. Identifying disease-specific binding properties of affected Aß carriers may elucidate pathogenic aspects and open up a novel field for therapeutic approaches.