Cerebrospinal fluid AΒ
            42
            , total tau, and phosphorylated tau in the evaluation of Alzheimer’s dementia: Experience from a commercial reference laboratory

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.

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

Journal of Neurodegenerative Diseases ◽

10.1155/2013/679089 ◽

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.

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P4-180: BEHAVIORAL CORRELATES OF CEREBROSPINAL FLUID BIOMARKERS ACCORDING TO APOE-ε4 CARRIER STATUS IN DEMENTIA WITH LEWY BODIES COMPARED WITH ALZHEIMER'S DEMENTIA AND COGNITIVELY HEALTHY PEOPLE

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.06.3842 ◽

2019 ◽

Vol 15 ◽

pp. P1344-P1345

Author(s):

Fabricio Ferreira de Oliveira ◽

Marjorie Câmara Miraldo ◽

Eduardo Ferreira Castro-Neto ◽

Fernando Chiodini Machado ◽

Sandro Soares de Almeida ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Alzheimer’S Dementia ◽

Healthy People ◽

Carrier Status ◽

Behavioral Correlates ◽

Alzheimer's Dementia ◽

Apoe Ε4 ◽

Cerebrospinal Fluid Biomarkers

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Do cerebrospinal fluid transfer methods affect measured amyloid β42, total tau, and phosphorylated tau in clinical practice?

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring ◽

10.1016/j.dadm.2015.06.003 ◽

2015 ◽

Vol 1 (3) ◽

pp. 380-384 ◽

Cited By ~ 4

Author(s):

Ross W. Paterson ◽

Jamie Toombs ◽

Miles D. Chapman ◽

Jennifer M. Nicholas ◽

Amanda J. Heslegrave ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Clinical Practice ◽

Phosphorylated Tau ◽

Total Tau ◽

Fluid Transfer

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Total tau and Phosphorylated tau 181 Levels in the Cerebrospinal Fluid of Patients With Frontotemporal Dementia Due to P301L and G272V tau Mutations

Archives of Neurology ◽

10.1001/archneur.60.9.1209 ◽

2003 ◽

Vol 60 (9) ◽

Cited By ~ 43

Author(s):

Sonia M. Rosso ◽

Esther van Herpen ◽

Yolande A. L. Pijnenburg ◽

Niki S. M. Schoonenboom ◽

Philip Scheltens ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Frontotemporal Dementia ◽

Phosphorylated Tau ◽

Total Tau ◽

Phosphorylated Tau 181

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P1-145: A PROSPECTIVE, SYSTEMATIC LITERATURE REVIEW AND META-ANALYSES TO EVALUATE CEREBROSPINAL FLUID (CSF) PHOSPHORYLATED TAU (P-TAU) AND TOTAL TAU (T-TAU) AS BIOMARKERS OF ALZHEIMER'S DISEASE PROGRESSION

Alzheimer s & Dementia ◽

10.1016/j.jalz.2014.05.382 ◽

2014 ◽

Vol 10 ◽

pp. P353-P353

Author(s):

Enchi Liu ◽

Ajibade O. Ashaye ◽

Karin Travers ◽

Lauren Strand ◽

Kelly Olsson ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Literature Review ◽

Disease Progression ◽

Systematic Literature Review ◽

Phosphorylated Tau ◽

Total Tau ◽

Meta Analyses ◽

T Tau

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Potential Fluid Biomarkers for the Diagnosis of Mild Cognitive Impairment

International Journal of Molecular Sciences ◽

10.3390/ijms20174149 ◽

2019 ◽

Vol 20 (17) ◽

pp. 4149 ◽

Cited By ~ 11

Author(s):

Vo Van Giau ◽

Eva Bagyinszky ◽

Seong Soo A. An

Keyword(s):

Cerebrospinal Fluid ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Phosphorylated Tau ◽

Transitional State ◽

Total Tau ◽

Current State ◽

Risk Of Progression ◽

Csf Levels ◽

Potential Fluid

Mild cognitive impairment (MCI) is characterized by a level of cognitive impairment that is lower than normal for a person’s age, but a higher function than that that observed in a demented person. MCI represents a transitional state between normal aging and dementia disorders, especially Alzheimer’s disease (AD). Much effort has been made towards determining the prognosis of a person with MCI who will convert to AD. It is now clear that cerebrospinal fluid (CSF) levels of Aβ40, Aβ42, total tau and phosphorylated tau are useful for predicting the risk of progression from MCI to AD. This review highlights the advantages of the current blood-based biomarkers in MCI, and discusses some of these challenges, with an emphasis on recent studies to provide an overview of the current state of MCI.

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