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Background: Alzheimer's disease (AD) may present with pure (typical or atypical) and mixed phenotypes, sometimes causing difficulties in (differential) diagnosis. In order to achieve a diagnostic accuracy as high as possible, the diagnosis of AD during life depends on various biomarkers, including the cerebrospinal fluid (CSF) biomarkers. Methods: Classical CSF AD biomarkers were determined in a total of 61 patients, classified as both beta amyloid- and tau-positive A+T+ (or A+T1+ according to the recently revised Alzheimer Association criteria for diagnosis and staging of AD). Twenty one of these patients fulfilled the criteria for mixed AD (mixed with Lewy bodies, cerebrovascular disease, or normal pressure hydrocephalus), whilst 40 had pure AD. Results: Patients did not differ with respect to gender, education, disease duration, and cognitive status. After controlling for confounding factors, no difference was observed between mixed and pure AD groups in Aβ42 or Aβ42/Aβ40 levels. Although by definition, patients of both groups had abnormal (increased) levels of phospho-tau181, the mixed AD group presented with lower (less abnormal) levels of phospho-tau181 and total tau as compared to the pure group. Conclusions: In patients with AD of comparable cognitive status, mixed AD cases may present with lower levels of tau proteins and, if close to the cut-off values, diagnostic uncertainty may be increased. [ABSTRACT FROM AUTHOR]

Background: Alzheimer’s disease (AD) may present with pure (typical or atypical) and mixed phenotypes, sometimes causing difficulties in (differential) diagnosis. In order to achieve a diagnostic accuracy as high as possible, the diagnosis of AD during life depends on various biomarkers, including the cerebrospinal fluid (CSF) biomarkers. Methods: Classical CSF AD biomarkers were determined in a total of 61 patients, classified as both beta amyloid- and tau-positive A+T+ (or A+T1+ according to the recently revised Alzheimer Association criteria for diagnosis and staging of AD). Twenty one of these patients fulfilled the criteria for mixed AD (mixed with Lewy bodies, cerebrovascular disease, or normal pressure hydrocephalus), whilst 40 had pure AD. Results: Patients did not differ with respect to gender, education, disease duration, and cognitive status. After controlling for confounding factors, no difference was observed between mixed and pure AD groups in Aβ42 or Aβ42/Aβ40 levels. Although by definition, patients of both groups had abnormal (increased) levels of phospho-tau181, the mixed AD group presented with lower (less abnormal) levels of phospho-tau181 and total tau as compared to the pure group. Conclusions: In patients with AD of comparable cognitive status, mixed AD cases may present with lower levels of tau proteins and, if close to the cut-off values, diagnostic uncertainty may be increased.

Cerebrospinal fluid (CSF) biomarkers remain the gold standard for fluid-biomarker-based diagnosis of Alzheimer's disease (AD) during life. Plasma biomarkers avoid lumbar puncture and allow repeated sampling. Changes of plasma phospho-tau-181 in AD are of comparable magnitude and seem to parallel the changes in CSF, may occur in preclinical or predementia stages of the disease, and may differentiate AD from other causes of dementia with adequate accuracy. Plasma phospho-tau-181 may offer a useful alternative to CSF phospho-tau determination, but work still has to be done concerning the optimal method of determination with the highest combination of sensitivity and specificity and cost-effect parameters. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) biomarkers remain the gold standard for fluid-biomarker-based diagnosis of Alzheimer’s disease (AD) during life. Plasma biomarkers avoid lumbar puncture and allow repeated sampling. Changes of plasma phospho-tau-181 in AD are of comparable magnitude and seem to parallel the changes in CSF, may occur in preclinical or predementia stages of the disease, and may differentiate AD from other causes of dementia with adequate accuracy. Plasma phospho-tau-181 may offer a useful alternative to CSF phospho-tau determination, but work still has to be done concerning the optimal method of determination with the highest combination of sensitivity and specificity and cost-effect parameters.

Analysis of classical cerebrospinal fluid biomarkers, especially when incorporated in a classification/diagnostic system such as the AT(N), may offer a significant diagnostic tool allowing correct identification of Alzheimer’s disease during life. We describe four patients with more or less atypical or mixed clinical presentation, in which the classical cerebrospinal fluid biomarkers amyloid peptide with 42 and 40 amino acids (Aβ42 and Aβ40, respectively), phospho-tau (τP-181) and total tau (τΤ) were measured. Despite the unusual clinical presentation, the biomarker profile was compatible with Alzheimer’s disease in all four patients. The measurement of classical biomarkers in the cerebrospinal fluid may be a useful tool in identifying the biochemical fingerprints of Alzheimer’s disease, especially currently, due to the recent approval of the first disease-modifying treatment, allowing not only typical but also atypical cases to be enrolled in trials of such treatments.

Analysis of classical cerebrospinal fluid biomarkers, especially when incorporated in a classification/diagnostic system such as the AT(N), may offer a significant diagnostic tool allowing correct identification of Alzheimer's disease during life. We describe four patients with more or less atypical or mixed clinical presentation, in which the classical cerebrospinal fluid biomarkers amyloid peptide with 42 and 40 amino acids (Aβ42 and Aβ40, respectively), phospho-tau (τP-181) and total tau (τΤ) were measured. Despite the unusual clinical presentation, the biomarker profile was compatible with Alzheimer's disease in all four patients. The measurement of classical biomarkers in the cerebrospinal fluid may be a useful tool in identifying the biochemical fingerprints of Alzheimer's disease, especially currently, due to the recent approval of the first disease-modifying treatment, allowing not only typical but also atypical cases to be enrolled in trials of such treatments. [ABSTRACT FROM AUTHOR]