Cerebrospinal Fluid Tau Levels Increase with Age in Healthy Individuals

Blomberg, Mari; Jensen, M.; Basun, Hans; Lannfelt, Lars; Wahlund, Lars‐Olof

doi:10.1159/000051246

Cited by 45 publications

(31 citation statements)

References 29 publications

(54 reference statements)

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“…Associations between CSF levels of tau, P-tau-181 and NfL with age were present in the control group. An age-related increase of tau has been described by others and in our study could be explained by the wide range of ages within the control group [29,30] .…”

Section: Discussionsupporting

confidence: 78%

CSF Neurofilaments in Frontotemporal Dementia Compared with Early Onset Alzheimer’s Disease and Controls

Pijnenburg¹,

Janssen

Schoonenboom³

et al. 2007

Dement Geriatr Cogn Disord

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Background: Frontotemporal dementia (FTD) is pathologically heterogeneous, sometimes revealing intraneuronal inclusions of neurofilaments. We therefore measured CSF neurofilament profiles in patients with FTD, patients with early onset Alzheimer’s disease (EAD) and healthy control subjects to explore the discriminative potential of CSF neurofilaments compared with the existing CSF biomarkers amyloid-β(1–42), tau and tau phosphorylated at threonine-181. Methods: CSF levels of light chain, heavy chain and hyperphosphorylated heavy chain neurofilaments (NfL, t-NfH and P-NfH) were compared between 17 subjects with FTD, 20 with EAD and 25 cognitively healthy controls. Results: A subgroup of FTD patients had remarkably high CSF levels of both NfL and NfH. The degree of NfH phosphorylation was increased in FTD compared to both other groups. The levels of CSF NfL were significantly higher in EAD compared to controls. Conclusion: Differences in CSF biomarker profiles might reflect differential involvement of neurofilaments and tau in FTD and EAD. The subgroup of FTD patients with high CSF neurofilament levels may have a different neuropathological substrate and future studies addressing this specific issue are needed.

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Section: Discussionsupporting

confidence: 78%

CSF Neurofilaments in Frontotemporal Dementia Compared with Early Onset Alzheimer’s Disease and Controls

Pijnenburg¹,

Janssen

Schoonenboom³

et al. 2007

Dement Geriatr Cogn Disord

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“…CSF T-tau is less specific for AD than CSF Aβ42. CSF T-tau reflects multiple degenerative processes, such as advancing age [23] and Lewy body disease [24], rapid cognitive decline and mortality in severe dementia [25]. Our study shows that both CSF Aβ42 and CSF T-tau are related to mortality among very old individuals independently of dementia status.…”

Section: Discussionmentioning

confidence: 78%

Amyloid β42 and Total Tau Levels in Cerebrospinal Fluid Associate with Survival in an 85-Year-Old Population-Based Cohort Followed until Death

Ribbe

Kern

Hansson

et al. 2019

Dement Geriatr Cogn Disord

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Background: Dementia of Alzheimer’s type (AD) is related to decreased survival. It is not clear whether also biological markers of AD are related to mortality. Low levels of amyloid beta-42 (Aβ42) and high levels of total tau (T-tau) protein in cerebrospinal fluid (CSF) are established biomarkers for AD. Objective: Our aim was to investigate whether levels of Aβ42 and T-tau are associated with survival among octogenarians independently of dementia status. Methods: Sixty-five 85-year-olds underwent lumbar puncture and were followed with repeated neuropsychiatric examinations until death. Results: Lower CSF Aβ42 (p = 0.010) and higher CSF T-tau (p = 0.005) at the age of 85 were associated with lower survival independently of dementia status at baseline and follow-up. Low CSF Aβ42 and high CSF T-tau were also related to baseline dementia at the age of 85 years, and lower CSF Aβ42 with increased dementia incidence during the first 3 years of follow-up. Conclusions: Biological markers of AD are associated with mortality in octogenarians. The reason for this needs further study. Our findings highlight the importance to consider the competing risk of death when evaluating biological markers of AD in the very old.

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“…CSF Ab 42 concentrations do not correlate with age. 47,48 However, a positive correlation with age was observed for CSF tau concentrations (r=0Í44^0Í46), 23,49 although this was not con¢rmed in another study. 37 Employing widely used commercial assays, the reference values for tau in healthy individuals (n=231) were de¢ned as: 5300 pg/mL (21^50 years); 5450 pg/mL (51^70 years); 5500 pg/ mL (71^93 years), whereas the Ab 42 concentration was constant (4500 pg/mL) over a wide age range.…”

Section: Correlations Of Csf Ab 42 and Tau With Age Severity And Durmentioning

confidence: 82%

“…21 This was con¢rmed in two other studies with AD patients (n=82^84) 24,57 and in a study with non-demented subjects (n=64). 48 CSF concentrations of tau were not a¡ected by ApoE genotype in relatively small study groups of either AD patients or healthy individuals 15,29,49,52 (n=19^65). In the same large AD group as above 21 (n=121), it was found, however, that tau levels were higher in AD patients carrying the e4 allele than in those without, whereas in control cases (n=39) no such correlation was observed.…”

Section: Effects Of Apolipoprotein Ementioning

confidence: 93%

Brain-specific proteins in cerebrospinal fluid for the diagnosis of neurodegenerative diseases

Verbeek¹,

Jong²,

Kremer³

2003

Ann Clin Biochem

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Neurodegenerative disorders have traditionally been classi ed according to clinical criteria, e.g. as dementia syndromes (the best known is Alzheimer's disease) or as movement disorders (e.g. Parkinson's disease). Another subdivision is based on recent insights into the respective pathogenetic mechanisms, leading to the recognition of so-called tauopathies and a-synucleinopathies. It is this increased knowledge of the underlying (neuro)pathological mechanisms that has sparked interest in studies aimed at the identi cation of disease-speci c biomarkers in cerebrospinal uid (CSF) for this eld of neurological disorders. This review deals with the recent progress that has been made in identi cation, quanti cation and subsequent validation of brain-speci c proteins in CSF for the diagnosis of various neurodegenerative disorders. Development of disease-speci c CSF biomarkers will undoubtedly add to the process of differential diagnosis early in the course of the disease.

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Cerebrospinal Fluid Tau Levels Increase with Age in Healthy Individuals

Cited by 45 publications

References 29 publications

CSF Neurofilaments in Frontotemporal Dementia Compared with Early Onset Alzheimer’s Disease and Controls

CSF Neurofilaments in Frontotemporal Dementia Compared with Early Onset Alzheimer’s Disease and Controls

Amyloid β42 and Total Tau Levels in Cerebrospinal Fluid Associate with Survival in an 85-Year-Old Population-Based Cohort Followed until Death

Brain-specific proteins in cerebrospinal fluid for the diagnosis of neurodegenerative diseases

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