scholarly journals Baseline cerebrospinal fluid biomarkers of amyloidosis, phosphorylated tau, and total tau relate to greater longitudinal atrophy in regions susceptible to Alzheimer’s disease‐related neurodegeneration

2020 ◽  
Vol 16 (S5) ◽  
Author(s):  
Elizabeth E. Moore ◽  
Omair A. Khan ◽  
Dandan Liu ◽  
Kimberly R. Pechman ◽  
Lealani Mae Y. Acosta ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Phosphorylated Tau ◽  
Total Tau ◽  
Cerebrospinal Fluid Biomarkers

scholarly journals On the design of early-phase Alzheimer’s disease clinical trials with cerebrospinal fluid tau outcomes

2021 ◽  
pp. 174077452110344
Author(s):  
Michelle M Nuño ◽  
Joshua D Grill ◽  
Daniel L Gillen ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cerebrospinal Fluid ◽  
Phosphorylated Tau ◽  
Inclusion Criteria ◽  
Eligibility Criteria ◽  
Total Tau ◽  
Prodromal Alzheimer’S Disease ◽  
Study Power

Background/Aims: The focus of Alzheimer’s disease studies has shifted to earlier disease stages, including mild cognitive impairment. Biomarker inclusion criteria are often incorporated into mild cognitive impairment clinical trials to identify individuals with “prodromal Alzheimer’s disease” to ensure appropriate drug targets and enrich for participants likely to develop Alzheimer’s disease dementia. The use of these eligibility criteria may affect study power. Methods: We investigated outcome variability and study power in the setting of proof-of-concept prodromal Alzheimer’s disease trials that incorporate cerebrospinal fluid levels of total tau (t-tau) and phosphorylated (p-tau) as primary outcomes and how differing biomarker inclusion criteria affect power. We used data from the Alzheimer’s Disease Neuroimaging Initiative to model trial scenarios and to estimate the variance and within-subject correlation of total and phosphorylated tau. These estimates were then used to investigate the differences in study power for trials considering these two surrogate outcomes. Results: Patient characteristics were similar for all eligibility criteria. The lowest outcome variance and highest within-subject correlation were obtained when phosphorylated tau was used as an eligibility criterion, compared to amyloid beta or total tau, regardless of whether total tau or phosphorylated tau were used as primary outcomes. Power increased when eligibility criteria were broadened to allow for enrollment of subjects with either low amyloid beta or high phosphorylated tau. Conclusion: Specific biomarker inclusion criteria may impact statistical power in trials using total tau or phosphorylated tau as the primary outcome. In concert with other important considerations such as treatment target and population of clinical interest, these results may have implications to the integrity and efficiency of prodromal Alzheimer’s disease trial designs.

scholarly journals Cerebrospinal Fluid Biomarkers for Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Yui Nakayama ◽  
Satoru Morimoto ◽  
Misao Yoneda ◽  
Shigeki Kuzuhara ◽  
Yasumasa Kokubo
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Phosphorylated Tau ◽  
Total Tau ◽  
Lateral Sclerosis

Objective. Amyotrophic lateral sclerosis/parkinsonism-dementia complex is classified as one of the tauopathies. Methods. The total tau, phosphorylated tau, and amyloid β42 levels were assayed in cerebrospinal fluid from patients with Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (), Alzheimer’s disease (), Parkinson’s disease (), amyotrophic lateral sclerosis (), and controls () using specific enzyme-linked immunosorbent assay methods. Results. Total tau and phosphorylated tau did not increase and amyloid β42 was relatively reduced in Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex. Relatively reduced amyloid β42 might discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from amyotrophic lateral sclerosis and Parkinson’s disease, and the ratios of phosphorylated-tau to amyloid β42 could discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer’s disease. Conclusions. Cerebrospinal fluid analysis may be useful to differentiate amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease.

scholarly journals Clinical and biological predictors of Alzheimer's disease in patients with amnestic mild cognitive impairment

2010 ◽  
Vol 32 (3) ◽  
pp. 216-222 ◽  
Author(s):  
Orestes V. Forlenza ◽  
Breno S. Diniz ◽  
Leda L. Talib ◽  
Marcia Radanovic ◽  
Monica S. Yassuda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amnestic Mild Cognitive Impairment ◽  
Total Tau ◽  
Cerebrospinal Fluid Biomarkers ◽  
Antidementia Drugs ◽  
Beta Peptide

OBJECTIVE: To identify predictors of the progression from pre-dementia stages of cognitive impairment in Alzheimer's disease is relevant to clinical management and to substantiate the decision of prescribing antidementia drugs. METHOD: Longitudinal study of a cohort of elderly adults with amnestic mild cognitive impairment and healthy controls, carried out to estimate the risk and characterize predictors of the progression to Alzheimer's disease. RESULTS: Patients with amnestic mild cognitive impairment had a higher risk to develop Alzheimer's disease during follow-up (odds ratio = 4.5, CI95% [1.3-13.6], p = 0.010). At baseline, older age, lower scores on memory tests and presence of the APOE*4 allele predicted the progression from amnestic mild cognitive impairment to Alzheimer's disease. In a sub sample of amnestic mild cognitive impairment patients, those who progressed to Alzheimer's disease had lower cerebrospinal fluid concentrations of amyloid-beta peptide (Aβ42, p = 0.020) and higher concentrations of total TAU (p = 0.030) and phosphorylated TAU (p = 0.010), as compared to non-converters. DISCUSSION: This is the first Brazilian study to report cerebrospinal fluid biomarkers in the prediction of the conversion from MCI to Alzheimer's disease. Our data are in accordance with those reported in other settings. The measurement of cerebrospinal fluid total-TAU, phospho-TAU and Aβ42 may help identify patients with mild cognitive impairment at higher risk for developing Alzheimer's disease.

scholarly journals ATN status in amnestic and non-amnestic Alzheimer’s disease and frontotemporal lobar degeneration

2019 ◽  
Author(s):  
Katheryn A.Q. Cousins ◽  
David J. Irwin ◽  
David A. Wolk ◽  
Edward B. Lee ◽  
Leslie M.J. Shaw ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Frontotemporal Lobar Degeneration ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Amyloid Β ◽  
Phosphorylated Tau ◽  
Total Tau ◽  
Operating Characteristic Curve

AbstractUnder the ATN framework, cerebrospinal fluid analytes provide evidence of the presence or absence of Alzheimer’s disease pathological hallmarks: amyloid plaques (A), phosphorylated tau (T), and accompanying neurodegeneration (N). Still, differences in cerebrospinal fluid levels across amnestic and non-amnestic variants or due to co-occurring pathologies might lead to misdiagnoses. We assess the diagnostic accuracy of cerebrospinal fluid markers for amyloid, tau, and neurodegeneration in an autopsy cohort of 118 Alzheimer’s disease patients (98 amnestic; 20 non-amnestic) and 64 frontotemporal lobar degeneration patients (five amnestic; 59 non-amnestic). We calculated between-group differences in cerebrospinal fluid concentrations of amyloid-β1–42 peptide, tau protein phosphorylated at threonine 181, total tau, and the ratio of phosphorylated tau to amyloid-β1–42. Results show that non-amnestic Alzheimer’s disease patients were less likely to be correctly classified under the ATN framework using independent, published biomarker cutoffs for positivity. Amyloid-β1–42 did not differ between amnestic and non-amnestic Alzheimer’s disease, and receiver operating characteristic curve analyses indicated that amyloid-β1–42 was equally effective in discriminating both groups from frontotemporal lobar degeneration. However, cerebrospinal fluid concentrations of phosphorylated tau, total tau, and the ratio of phosphorylated tau to amyloid-β1–42 were significantly lower in non-amnestic compared to amnestic Alzheimer’s disease patients. Receiver operating characteristic curve analyses for these markers showed reduced area under the curve when discriminating non-amnestic Alzheimer’s disease from frontotemporal lobar degeneration, compared to discrimination of amnestic Alzheimer’s disease from frontotemporal lobar degeneration. In addition, the ATN framework was relatively insensitive to frontotemporal lobar degeneration, and these patients were likely to be classified as having normal biomarkers or biomarkers suggestive of primary Alzheimer’s disease pathology. We conclude that amyloid-β1–42 maintains high sensitivity to A status, although with lower specificity, and this single biomarker provides better sensitivity to non-amnestic Alzheimer’s disease than either the ATN framework or the phosphorylated-tau/amyloid-β1–42 ratio. In contrast, T and N status biomarkers differed between amnestic and non-amnestic Alzheimer’s disease; standard cutoffs for phosphorylated tau and total tau may thus result in misclassifications for non-amnestic Alzheimer’s patients. Consideration of clinical syndrome may help improve the accuracy of ATN designations for identifying true non-amnestic Alzheimer’s disease.Abbreviated SummaryCousins et al. assess the 2018 ATN framework and find that non-amnestic patients with Alzheimer’s disease (AD) have lower cerebrospinal fluid (CSF) phosphorylated tau and total tau than amnestic AD, while CSF amyloid-β accurately stratifies both non-amnestic and amnestic AD from frontotemporal lobar degeneration.

scholarly journals From Cerebrospinal Fluid Neurochemistry to Clinical Diagnosis of Alzheimer’s Disease in the Era of Anti-Amyloid Treatments. Report of Four Patients

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1376
Author(s):  
Ioanna Tsantzali ◽  
Fotini Boufidou ◽  
Eleni Sideri ◽  
Antonis Mavromatos ◽  
Myrto G. Papaioannou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Clinical Presentation ◽  
Diagnostic System ◽  
Amyloid Peptide ◽  
Correct Identification ◽  
Total Tau ◽  
Cerebrospinal Fluid Biomarkers ◽  
Disease Modifying Treatment

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.

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