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1.  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 Aβ42, 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 Aβ42 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.
doi:10.1177/1756285612455367
PMCID: PMC3487531  PMID: 23139704
Alzheimer’s disease; biomarker; blood; cerebrospinal fluid; dementia
2.  Cerebrospinal fluid amyloid-β 2-42 is decreased in Alzheimer’s, but not in frontotemporal dementia 
Journal of Neural Transmission  2012;119(7):805-813.
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) Aβ2-42 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 Aβ2-42 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 Aβ-SDS-PAGE/immunoblot, allowing the quantification of peptides 1-38ox, 2-40 and 2-42 along with Aβ 1-37, 1-38, 1-39, 1-40, 1-40ox and 1-42. CSF Aβ1-42 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. Aβ1-38 was decreased in FTD as compared to NDC and AD. For differentiating AD from FTD, Aβ1-42 demonstrated sufficient diagnostic accuracies only when combined with Aβ1-38. Aβ2-42 yielded diagnostic accuracies of over 85 % as a single marker. These accuracy figures could be improved by combining Aβ2-42 to Aβ1-38. Aβ2-42 seems to be a promising biomarker for differentiating AD from other degenerative dementias, such as FTD.
doi:10.1007/s00702-012-0801-3
PMCID: PMC3605494  PMID: 22527776
Alzheimer’s dementia; Frontotemporal dementia; Cerebrospinal fluid; Aminoterminally truncated; Amyloid-β peptides; Aβ2-42
3.  Combined Analysis of CSF Tau, Aβ42, Aβ1–42% and Aβ1–40ox% in Alzheimer's Disease, Dementia with Lewy Bodies and Parkinson's Disease Dementia 
We studied the diagnostic value of CSF Aβ42/tau versus low Aβ1–42% and high Aβ1–40ox% 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 Aβ-SDS-PAGE/immunoblot and ELISAs (Aβ42 and tau). Aβ42/tau lacked specificity in discriminating AD from DLB and PDD. Best discriminating biomarkers were Aβ1–42% and Aβ1–40ox% for AD and DLB, respectively. AD and DLB could be differentiated by both Aβ1–42% and Aβ1–40ox% with an accuracy of 80% at minimum. Thus, we consider Aβ1–42% and Aβ1–40ox% to be useful biomarkers for AD and DLB, respectively. We propose further studies on the integration of Aβ1–42% and Aβ1–40ox% into conventional assay formats. Moreover, future studies should investigate the combination of Aβ1–40ox% and CSF alpha-synuclein for the diagnosis of DLB.
doi:10.4061/2010/761571
PMCID: PMC2938459  PMID: 20862375

Results 1-3 (3)